IL-13 Induces Esophageal Remodeling and Expression by an Eosinophil-Independent, IL-13Rα2−Inhibited Pathway This information is current as of September 30, 2021. Li Zuo, Patricia C. Fulkerson, Fred D. Finkelman, Melissa Mingler, Christine A. Fischetti, Carine Blanchard and Marc E. Rothenberg J Immunol 2010; 185:660-669; Prepublished online 11 June 2010; Downloaded from doi: 10.4049/jimmunol.1000471 http://www.jimmunol.org/content/185/1/660 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2010/06/07/jimmunol.100047 Material 1.DC1 References This article cites 27 articles, 6 of which you can access for free at: http://www.jimmunol.org/content/185/1/660.full#ref-list-1

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The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2010 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology

IL-13 Induces Esophageal Remodeling and by an Eosinophil-Independent, IL-13Ra2–Inhibited Pathway

Li Zuo,* Patricia C. Fulkerson,* Fred D. Finkelman,† Melissa Mingler,* Christine A. Fischetti,* Carine Blanchard,* and Marc E. Rothenberg*

Eosinophilic esophagitis (EE) is an emerging disease associated with both food and respiratory allergy characterized by extensive esophageal tissue remodeling and abnormal esophageal gene expression, including increased IL-13. We investigated the ability of increased airway IL-13 to induce EE-like changes. Mice with pulmonary (but not esophageal) overexpression of IL-13 evidenced esophageal IL-13 accumulation and developed prominent esophageal remodeling with epithelial hyperplasia, angiogenesis, col- lagen deposition, and increased circumference. IL-13 induced notable changes in esophageal transcripts that overlapped with the human EE esophageal transcriptome. IL-13–induced esophageal eosinophilia was dependent on eotaxin-1 (but not eotaxin-2).

However, remodeling occurred independent of eosinophils as demonstrated by eosinophil lineage-deficient, IL-13 transgenic mice. Downloaded from IL-13–induced remodeling was significantly enhanced by IL-13Ra2 deletion, indicating an inhibitory effect of IL-13Ra2. In the murine system, there was partial overlap between IL-13–induced in the lung and esophagus, yet the transcriptomes were divergent at the tissue level. In human esophagus, IL-13 levels correlated with the magnitude of the EE transcriptome. In conclusion, inducible airway expression of IL-13 results in a pattern of esophageal gene expression and extensive tissue remodeling that resembles human EE. Notably, we identified a pathway that induces EE-like changes and is IL-13–driven, eosinophil-independent, and suppressed by IL-13Ra2. The Journal of Immunology, 2010, 185: 660–669. http://www.jimmunol.org/

sophageal eosinophilia occurs in a variety of disorders, the development of EE (5). In addition, eosinophilic inflammation including gastroesophageal reflux disease and primary eo- in the esophagus can be induced directly by intranasal or intra- E sinophilic esophagitis (EE) (1, 2). EE is an emerging dis- tracheal human or murine IL-13 (6) and can be blocked by anti- order that presents with gastroesophageal reflux disease-like human IL-13 Ab (6). In addition, aeroallergen-induced EE is de- symptoms (vomiting, abdominal pain, failure to thrive, dysphagia, pendent on IL-13, as assessed by failure of IL-13 gene-targeted and food impaction) but does not fully respond to acid neutralization mice to develop esophageal eosinophilia and epithelial hyperpla- therapy. Largely mediated by oral- and aero-Ag–induced esophageal sia (7). Based on these findings in mice, IL-13 may have a role in by guest on September 30, 2021 adaptive immunity, EE responds to anti-inflammatory agents (e.g., EE induction in humans. Indeed, IL-13 is overproduced in the glucocorticoids) and food Ag elimination diets. EE involves exten- esophagus of EE patients and is capable of inducing a gene ex- sive eosinophil accumulation in the proximal and distal esophagus pression profile in esophageal epithelial cells that partially over- and extensive tissue remodeling, including epithelial thickening and laps with the esophageal transcriptome present in EE patients (8). deposition, even in pediatric individuals (3). The IL-13–induced, epithelial cell-produced gene that is most The etiology of EE is poorly understood, but allergy has been overexpressed in the esophagus of EE patients is eotaxin-3,a implicated. In fact, the majority of EE patients have evidence of potent eosinophil chemokine and activating factor (8). Whether food and aeroallergen hypersensitivity as defined by skin prick IL-13 directly contributes to esophageal tissue pathology (inde- testing and in vitro lymphocyte responses (4). Previous studies pendent of eosinophils) has not been determined. Although IL-13 have shown that repeated challenge of mice with intranasal As- has been shown to be involved in the development of tissue pergillus fumigatus Ag induces lymphocyte-dependent EE remodeling in the lung (9) and intestine (10), its role in the de- changes, supporting the association between airway allergy and velopment of esophageal remodeling has not been examined. Ex- perimental models of aeroallergen and IL-13 delivery to the lung have shown that eosinophils contribute, at least in part, to esoph- *Division of Allergy and Immunology and †Division of Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229 ageal epithelial hyperplasia and collagen levels in the esophagus. Yet, IL-13 has also been shown to induce tissue remodeling by Received for publication February 16, 2010. Accepted for publication April 26, 2010. eosinophil-independent effects under a variety of conditions This work was supported in part by National Institutes of Health Grants R01 AI42242, R01 AI45898, R01 DK076893, P01 HL076383, P30 DK 0789392, T32 within multiple tissues (9–12). As such, it is relevant to determine AI 060515, and T32 DK 07727-12 and the Campaign Urging Research for Eosino- whether IL-13 is capable of directly or indirectly inducing esoph- philic Disease Foundation, the Buckeye and Food Allergy Project Foundation, and the ageal remodeling typical of EE and the relevance of this process American Association of Allergy and Immunology Food Allergy Initiative Award. to human EE. To test these possibilities, we used a murine, in- Address correspondence and reprint requests to Dr. Marc E.Rothenberg, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229- ducible, lung-specific IL-13 transgenic model, wherein IL-13 is 3039. E-mail address: [email protected] selectively overexpressed in the lungs in an externally regulated The online version of this article contains supplemental material. fashion after transgene induction with dietary doxycycline (9). We Abbreviations used in this paper: DOX, doxycycline; EE, eosinophilic esophagitis; aimed to determine the ability of chronic airway IL-13 stimulation EP, epithelial; KO, knockout; LP, lamina propria; L, lumen; MBP, major basic pro- to induce experimental EE with tissue remodeling, the mechanism tein; MM, muscularis mucosa; NL, normal. and receptors involved in disease development, and the applica- Copyright Ó 2010 by The American Association of Immunologists, Inc. 0022-1767/10/$16.00 bility of our results to human EE. www.jimmunol.org/cgi/doi/10.4049/jimmunol.1000471 The Journal of Immunology 661

Materials and Methods was used to determine the average number of PECAM-1 positive vessels Inducible, lung-specific IL-13 transgenic mice per high-power field in each group. Bitransgenic mice (CC10-iIL-13) were generated in which IL-13 was Determination of esophageal circumference expressed in a lung-specific manner that allowed for external regulation The esophagus was isolated by cutting the proximal end at the level of the of the transgene expression as previously described (13). CC10-iIL-13 cricoid ring and the distal end 2–5 mm above the stomach. It was then mice deficient in eosinophils, eotaxin-1, and eotaxin-2 were generated suspended in HBSS and longitudinally exposed on an agarose gel for the D by breeding the CC10-iIL-13 (FVB/n) with the dbl-GATA (BALB/c), measurement of esophageal circumference. eotaxin-1 (SVEV), and eotaxin-2 (SVEV) gene-targeted mice for three generations. Ddbl-GATA mice were generously provided by Drs. Alison Measurement of IL-13 and IL-13/soluble IL-13Ra2 complex Humbles and Craig Gerard (Children’s Hospital, Boston, MA). For all experiments, wild-type mice with the appropriate mixed backgrounds content of IL-13 and IL-13/soluble IL-13Ra2 complex was (FVB/N) were used as controls. Transgene expression was induced by determined by ELISA (14). For IL-13, an IL-13–specific ELISA kit feeding bitransgenic mice doxycycline-impregnated food (DOX) (625 (R&D Systems, Minneapolis, MN) was used to measure the protein mg/kg; Purina Mills, Richmond, IN). Animals were housed under specific level from homogenized tissue solutions. IL-13/soluble IL-13Ra2 pathogen-free conditions in accordance with institutional guidelines. complex was quantified using a capture ELISA method. Briefly, 96-well plates were coated with anti–IL-13 Ab (R&D Systems) overnight at 4˚C. Quantification of tissue eosinophils Samples of either blood serum or soluble extract of homogenized esoph- agus were applied to the plate and incubated at room temperature for 2 h. Esophageal eosinophils were detected using an immunohistochemical stain Wells were washed and then incubated at room temperature with biotiny- against murine eosinophilic major basic protein (MBP) as reported (9). lated anti-mouse IL-13Ra2 Ab (R&D Systems) for 2 h, streptavidin-HRP Endogenous peroxidase activity was quenched using a 0.3% hydrogen conjugate (R&D Systems) for 20 min, and solution (R&D Sys- peroxide in methanol solution. Tissue was then subjected to pepsin for 10 tems) for 20 min. Absorbance was read at 450 nm, and OD readings were Downloaded from min at 37˚C (DIGEST-ALLTM 3, Zymed Laboratories, San Francisco, converted to nanograms per milliliter. To determine the total IL-13Ra2 CA). Nonspecific binding was blocked using 3% goat serum in PBS for level, samples were presaturated with IL-13 prior to being added to the 2 h at room temperature, followed by the addition of rabbit anti-murine wells. A saturation percentage was calculated using the ratio of IL- MBP (1:8000) primary Ab (kindly provided by Dr. Jamie Lee, Mayo 13/soluble IL-13Ra2 complex divided by total IL-13Ra2. Clinic, Scottsdale, AZ), which was allowed to incubate overnight at 4˚C. Slides were incubated with biotinylated goat anti-rabbit (1:250) secondary Microarray analysis Ab for 40 min at room temperature, and then incubated with an avidin- peroxidase complex for 30 min (Vector Laboratories, Burlingame, CA). RNA from the esophagus or lung of inducible IL-13 transgenic mice obtained http://www.jimmunol.org/ Development of peroxidase reaction was achieved by incubating slides after 30 d of DOX or NO-DOX treatment was subjected to gene chip analysis with nickel diaminobenzidine-cobalt chloride solution (Vector Laborato- using MOE 430 2.0 chips as previously reported (15). Gene transcript levels ries) for 4 min at room temperature. Slides were then counterstained with were determined using algorithms in the Microarray Analysis Suite and nuclear fast red. Quantification of positive cells was performed using GeneSpring software (Silicon Genetics, Redwood City, CA). For compari- ImagePro Plus imaging software and results were reported as immunore- son with human EE, murine genes were translated to human homologs active cells per square millimeter. represented on the human U133 chip using GeneSpring software and com- pared with microarray results previously described (8, 15). Welch’s t test Epithelial thickness and collagen quantitation and fold change cutoff were performed. The correlation between IL-13 expression and levels of dysregulated genes were also analyzed using Epithelial thickness was determined by staining cross-sectioned esophageal GeneSpring software. Raw microarray data in GEO format is available samples with H&E. Quantitation of thickness was performed using Image- electronically with GEO Submission number GSE21267 at www.ncbi. by guest on September 30, 2021 Pro Plus imaging software by taking three to six lengthwise measurements nlm.nih.gov/geo/query/acc.cgi?acc=GSE21267. per slide from the lumen to the of each esophagus. Collagen deposition was determined by staining esophageal samples with Real-time quantitative PCR analysis trichrome and quantitated using ImagePro Plus imaging software. Colla- gen measurements are recorded as area of collagen staining per length of RNAsamplesfromthewholeesophagusweresubjectedtoreversetranscription basement membrane. analysis using SuperScript II reverse transcriptase (Invitrogen, Carlsbad, CA) according to manufacturer’s instructions. Real-time PCR analysis of trans- Analysis of epithelial cell proliferation genic IL-13 and rtTA levels was performed using the LightCycler 480 system in conjunction with the ready-to-use LightCycler 480 SYBR Green I 9 To determine the degree of epithelial cell proliferation, 5 -BrdU (Zymed Master reaction kit (Roche Diagnostic Systems, Branchburg, NJ). Results were Laboratories) incorporation analysis was performed according to previ- normalized to GAPDH cDNA. Amplification of cDNA was achieved using ously reported methods (6). In brief, DOX and untreated (NO-DOX) mice the following primers: transgenic IL-13 (205 bp), 59-ATGGCTGGCAACTA- 9 m were injected i.p. with 0.25 ml 5 -BrdU solution (0.75 g BrdU) 2 h before GAAGGC-39 and 59-CATCTACAGGACCCAGAGGA-39; rtTA (200 bp), 59- death. The esophagus was fixed with 10% neutral buffered formalin GCGCATTAGAGCTGCTTAATG-39 and 59-AAAATCTTGCCAGCTT- (Sigma-Aldrich, St. Louis, MO) for 24 h. After fixation, the tissue was TCCCC-39; eotaxin 1 (87 bp), 59-CCCAACACACTACTGAAGAGCT- m embedded in paraffin, and 5- m sections were processed using standard ACAA-39 and 69-TTTGCCCAACCTGGTCTTG-39; eotaxin 2 (280 bp), 59- histologic approaches. Tissue was digested with (0.125%) for 3 min TGTGACCATCCCCTCATCTTGC-39 and 59-AAACCTCGGTGCTATTG- at 37˚C, followed by incubation for 30 min at room temperature. Sections CCACG-39; human IL-13 (125 bp), 59-ACAGCCCTCAGGGAGCTCAT-39 were washed with PBS three times for 2 min and further incubated with and 59-TCAGGTTGATGCTCCATACCAT-39. monoclonal biotinylated anti-BrdU Ab for 60 min at room temperature. Negative controls included replacing the primary Ab with PBS, and pos- Statistical analysis itive controls were provided by the manufacturer. Cells with nuclear stain- ing for BrdU were detected with streptavidin-peroxidase and DAB Statistical significance comparing different sets of mice was determined by , substrate (Zymed Laboratories), followed by counterstaining with H&E. Student t test. The p values 0.05 were considered statistically significant. The BrdU+ cell quantitation was carried out with the assistance of digital SPSS software was used for the statistical analysis. morphometry as described previously for eosinophils. Results Assessment of angiogenesis Esophageal eosinophilia induced by pulmonary IL-13 Tissues were fixed, embedded, sectioned, and prepared as described pre- overexpression viously. Slides were trypsinized with 0.1% trypsin at 37˚C for 5 min (BD Difco, Franklin Lakes, NJ), incubated with 180 ml methyl alcohol and 3 ml Dietary DOX exposure of iIL-13 transgenic mice increased esoph- 30% hydrogen peroxide, blocked with 2% rabbit serum/PBS/Triton for 2 h, ageal eosinophilia ∼47-fold in iIL-13 transgenic mice (Fig. 1). and incubated overnight with rat anti-mouse CD31 (PECAM-1) Ab (BD Representative photomicrographs of untreated and DOX-treated Pharmingen 01951D, San Diego, CA) at 4˚C. Slides were then incubated with biotinylated rabbit anti-rat Ab (Vector Laboratory, BA-4001) for 30 mice stained with anti-MBP Ab to detect eosinophils are shown min, developed with ABC complex and DAB substrate, and counterstained in Fig. 1A and 1B, respectively. Eosinophils infiltrated all layers of with 0.1% nuclear fast red in 5% aluminum sulfate for 2 min. Morphometry the esophagus, including the muscularis mucosa, lamina propria, 662 IL-13 TRANSGENE-INDUCED EE

Morphometric analysis also showed that the esophageal cir- cumference was increased in DOX-treated mice (Fig. 3A,3B). DOX treatment increases esophageal IL-13 protein, but not IL-13 mRNA DOX treatment for 4 wk increased IL-13 protein nearly 1000-fold in the lungs and ∼8-fold in the esophagus of iIL-13 transgenic mice (Fig. 4A). Esophageal IL-13 peaked after 1 wk of DOX treatment and plateaued over the next 3 wk; whereas, pulmonary IL-13 continued to increase. IL-13 mRNA (measured using transgene-specific primers) increased in the lung but not the esophagus during the same period (Fig. 4B). DOX did not increase the expression of endogenous IL-13 mRNA (data not shown). The finding of increased transgenic IL-13 mRNA in the lung but not in the esophagus is consistent with the lung specificity of this IL-13 transgenic model. IL-13 induces marked in situ esophageal gene expression

FIGURE 1. IL-13 transgene-induced esophageal eosinophilia. The To define the molecular pathways induced by IL-13 in the esoph- Downloaded from esophagus of lung-specific IL-13 transgenic mice before (A) and after agus, we conducted a genome-wide microarray expression pro- (B) 4 wk of DOX exposure was stained with anti-MBP to identify eosino- file analysis of RNA isolated from the esophagus of IL-13 phils. Eosinophils are identifiable by dark immunostaining. The kinetics of transgenic mice that were exposed to DOX for 30 d and com- eosinophilia in the lung and esophagus of lung-specific IL-13 transgenic pared the gene transcript levels with age- and gender-matched mice is shown in C. Data are representative of three independent ex- transgenic mice that were not exposed to DOX, using methods periments with n = 6 mice per time point in each experiment. A and B, 3 previously reported (9). DOX-induced increases in IL-13 pro- Original magnification 100. EP, epithelial; L, lumen; LP, lamina propria; http://www.jimmunol.org/ MM, muscularis mucosa. tein were associated with a significant difference in 767 genes (p , 0.05) in the esophagus of transgenic mice. This amount constitutes 1.7% of the total transcriptome (45,101 transcripts). and epithelium. A kinetic analysis revealed that esophageal eosin- Among those 767 genes, 80 genes were modified $ 2fold ophilia peaked after 10 d of DOX and remained elevated during (Supplemental Table I). These genes cell-signaling pro- the 30-d experiment (Fig. 1C). The kinetics of esophageal and teins, cellular adhesion , and cell surface glycoproteins. pulmonary eosinophilia differed, but both returned to baseline Eosinophil-associated RNase, IL-1R–like 1, MAPK- levels by 3 wk after DOX withdrawal. Airway IL-13 did not in- 1, cholinergic , leukotriene C4 synthase, C3a receptor crease eosinophil levels in gastrointestinal segments distal to the

1, and IFN-induced transmembrane protein 6 were included in by guest on September 30, 2021 esophagus. For example, stomach eosinophil levels in untreated the IL-13–induced EE transcriptome. and DOX-treated mice were 12.4 6 7.6/mm2 and 14.1 6 4.9/mm2, Comparison of human EE and IL-13–induced murine EE respectively (p = 0.7). transcriptomes Esophageal tissue remodeling induced by increased pulmonary There were 283 genes in the murine IL-13–induced esophageal IL-13 expression transcriptome that overlapped with the human EE transcriptome DOX ingestion for 30 d induced marked inflammatory and (p , 0.05) (Supplemental Table II). The genes significantly con- remodeling changes in the esophagus of iIL-13 transgenic mice served between experimental EE and human EE are presented in (Fig. 2). Microscopically, DOX increased epithelial thickness a heat diagram (Fig. 5A). Functional analysis of genes that have (Fig. 2A,2B, Supplemental Fig. 1A) (this finding was also ob- .5-fold changes in either the human or murine system (Table I) served in tissue sections stained with anti-MBP, trichrome, BrdU, revealed their involvement in cell communication, cytokine–cytokine and anti-PECAM1, as shown in the Figs. 1, 2C–H). Increased receptor interaction, calcium signaling, histidine metabolism, com- epithelial thickness was accompanied by increased epithelial cell plement and cascades, JAK-STAT signaling, and arach- proliferation; there was an ∼2-fold increase in epithelial layer idonic acid metabolism. Notably, three CXC chemokines (CXCL1, 2, BrdU+ cell number, primarily associated with the basal zone and 6) were also among thosegenes that overlapped. Both CXCL1 and (Fig. 2C,2D, Supplemental Fig. 1B). CXCL2 have been shown to mediate IL-13–induced remodeling and inflammatory processes in the lung (12, 16). The effects of IL-13 on esophageal collagen and angiogenesis In the human system, 343 genes correlated with IL-13 mRNA were also assessed levels (Fig. 5B, Supplemental Table III). These included known An increase in the area of collagen-stained material (detected mostly IL-13–induced genes, such as eotaxin-3, as well as genes involved in the lamina propria in DOX-treated mice [Fig. 2E,2F]) was dem- in tissue remodeling, such as collagen type VIII alpha2, S, onstrated by trichrome staining and morphometric analysis (Supple- cathepsin C,andfibrinogen g-chain. Taken together, these results 2 mental Fig. 2A) (22 6 7.3 versus 43 6 5.1 m /mm basement suggest a role for IL-13 in esophageal remodeling in mouse and man. membrane [mean 6 SD n =4;p , 0.01]). In addition, DOX treatment increased the intensity of trichrome staining (using 1–4+ scoring) IL-13 induces esophageal eotaxin-1 and eotaxin-2, which are from 1.3 6 0.5 to 3.3 6 0.5 (mean 6 SD, n =4;p , 0.01). Staining required for esophageal eosinophilia with Ab to PECAM1, a vascular endothelial cell marker, revealed To investigate the mechanism of IL-13–induced eosinophilia in more blood vessels in DOX-treated mice (Fig. 2H) compared with this experimental EE model, we examined eotaxin production in control mice (Fig. 2G). This finding was confirmed by morphometric the lung and esophagus. Esophageal and pulmonary protein levels analysis (Supplemental Fig. 2B) and was mainly observed in the of eotaxin-1 (Fig. 6A) increased after 1 wk of DOX administration epithelial layer, just above the basement membrane regions. and remained elevated at 4 wk of DOX. The level of eotaxin-1 in The Journal of Immunology 663

FIGURE 2. IL-13 transgene-induced esopha- geal tissue remodeling. The esophagus of lung- specific IL-13 transgenic mice without (NO- DOX) (A, C, E, G) and after (B, D, F, H)4wk of DOX exposure was stained with H&E (A, B), for BrdU incorporation (C, D), trichrome (E, F), and anti–PECAM-1 (G, H). Representative images are shown of three independent experi- ments with n = 6 mice in each experiment. Orig- inal magnification for A, B, and E–H, 3100; C and D, 3400. EP, epithelial; L, lumen; LP, lam- ina propria; MM, muscularis mucosa.

the lung peaked by 4 wk of DOX administration. The level of These data indicate that IL-13–induced esophageal tissue eotaxin-2 (Fig. 6B) increased after 1 wk of DOX administration remodeling occurs independent of eosinophils in this animal model. Downloaded from and remained elevated at 4 wk in the lung and esophagus. The Increased accumulation of IL-13Rs level of eotaxin-1 and eotaxin-2 mRNA in the esophagus increased by 3.8- and 1.48-fold, respectively, between NO-DOX To further investigate the mechanism of IL-13–induced EE, we and DOX mice using gene chip analysis. To investigate if eotaxins examined the accumulation of IL-13Ra2 as well as IL-13/IL- were mediating IL-13–driven esophageal eosinophilia, we gen- 13Ra2 protein complexes because IL-13Ra2 has been shown to erated IL-13 transgenic mice that were deficient in eotaxin-1 or have a “decoy” effect on IL-13 function. Protein levels of free and http://www.jimmunol.org/ eotaxin-2. These studies revealed that IL-13–driven esophageal IL-13–bound sIL-13Ra2 were increased in both the blood (Fig. 8A) eosinophilia was primarily eotaxin-1 dependent (Fig. 6C). and the esophagus (Fig. 8B) after 4 wk of DOX. The data showed that essentially all the sIL-13Ra2 is complexed with IL-13 in the IL-13–induced esophageal remodeling is independent of esophagus, suggesting that free IL-13 may also be present. We also eosinophils tested the mRNA expression of IL-13Ra2 using real-time PCR. To determine the role of eosinophils in promoting the tissue remodeling seen in the iIL-13 transgenic mice, we examined triple transgenic mice [CC10/IL-13/GATA-1 knockout (KO)]. These mice express iIL-13 but lack the eosinophil lineage because of deletion of by guest on September 30, 2021 the double palindromic site in the GATA1 promoter (DdblGATA). These triple transgenic mice had no esophageal eosinophila after DOX induction for 4 wk (Fig. 7A) but still developed the same de- gree of tissue remodeling, including epithelial thickness (Fig. 7B), collagen deposition (Fig. 7C), and cellular hyperplasia (Fig. 7D).

FIGURE 4. IL-13 accumulation and expression in the esophagus and lung. Protein levels of IL-13 from pulmonary and esophageal tissue (n =8 mice for each group) following a time course of DOX exposure were measured by ELISA (A). The expression of IL-13 mRNA in the FIGURE 3. Esophageal circumference. The excised esophagus without esophagus and lung after 4 wk of DOX versus NO-DOX exposure is (NO-DOX) and after DOX exposure is shown in (A). Quantitative assess- shown. Real-time PCR analysis of IL-13 expression level is performed ment of the esophageal circumference is shown in (B). The results are and results are normalized to GAPDH cDNA (B). The results are the presented as mean 6 SD, n = 6 mice and the experiment was repeated summary of three independent experiments, reported as mean 6 SD independently at least three times. with n = 6 mice for each group or time point in each experiment. 664 IL-13 TRANSGENE-INDUCED EE

FIGURE 5. A, Esophageal transcript profile of lung-specific IL-13 transgenic mice. Microarray analysis of the lung and esophagus in doxycycline-treated CC10-rtTa (tet on)–IL13 transgenic mice and comparison with the human EE esophagus are shown. Cluster tree analysis of IL-13 transgenic esophagus and Downloaded from human EE. The 283 genes presented in the heat diagram (standard correlation) correspond to genes significantly different in experimental EE (p , 0.01) and human EE (p , 0.01) compared with their respective controls (NO-DOX and normal [NL] patient esophageal biopsies). Each line represents a separate individual. Upregulated and downregulated genes are shown in red and blue, respectively. B, The correlation between IL-13 expression and dysregulated genes. The 343 genes correlated with eosinophil levels (based on Spearman correlation) are shown in the gene tree format. Samples are organized in the order of increased IL-13 expression (from left to right) with each sample normalized for GAPDH expression. This data represents samples from a single patient, but it was repeatable in different patient samples. http://www.jimmunol.org/

Although DOX ingestion significantly increased pulmonary IL- (Fig. 9B), collagen deposition (Fig. 9C), and esophageal circum- 13Ra2 expression (p , 0.05), it had no significant effect on IL- ference (Fig, 9D). Esophageal tissue eosinophilia, however, was 13Ra2 expression in the esophagus (p = 0.15) (data not shown). similarly induced by IL-13 in IL-13Ra2–deficient and IL-13Ra2– sufficient mice (Fig. 9A). The increased esophageal remodeling, Inhibitory effect of IL-13Ra2 on esophageal tissue remodeling lung inflammation, and tissue necrosis induced by transgenic in lung-specific, IL-13 transgenic mice IL-13 in IL-13Ra2–deficient mice (not shown) was accompanied IL-13Ra2 has been described as both an IL-13 antagonist and by increased weight loss and death (Fig. 10). a mediator of IL-13–induced fibrosis (17, 18). To investigate the by guest on September 30, 2021 role of IL-13Ra2 in EE, we generated triple transgenic mice that Comparison of the IL-13–induced pulmonary and esophageal overexpressed CC10/IL-13 and were genetically deficient in IL- transcriptomes 13Ra2. DOX-induced IL-13 stimulated more severe esophageal We aimed to define molecular pathways that would distinguish remodeling in IL-13Ra2–deficient mice than in IL-13Ra2– pulmonary and esophageal responses induced by IL-13, especially sufficient mice (Fig. 9); there was increased epithelial thickness because IL-13–induced remodeling is eosinophil-dependent in the

Table I. Comparison of human EE and IL-13–induced murine EE transcriptomes

Affy No. NO DOX versus DOX NL versus EE Symbol Gene Name 207328_at 78.97 21.27 ALOX15 Arachidonate 15-lipoxygenase 204470_at 21.58 17.41 CXCL1 Chemokine (C-X-C motif) ligand 1 206336_at 3.526 9.173 CXCL6 Chemokine (C-X-C motif) ligand 6 206529_x_at 6.125 8.25 SLC26A4 Solute carrier family 26, member 4 204580_at 42.84 7.781 MMP12 Matrix 12 207134_x_at 1.313 7.732 TPSB2 b 2 209301_at 4.088 6.847 CA2 Carbonic anhydrase II 203854_at 3.346 6.522 IF I factor (complement) 205579_at 4.06 5.666 HRH1 Histamine receptor H1 206172_at 5.426 5.12 IL13RA2 IL 13R, a 2 205681_at 6.3 3 246 BCL2A1 BCL2- related protein A1 207067_s_at 5.76 3.141 HDC Histidine decarboxylase 206134_at 5.073 2.853 ADAMDEC1 ADAM-like, decysin 1 223502_s_at 7.902 2.073 TNFSF13B TNF superfamily, member 13b 209875_s_at 9.593 1.795 SPP1 Secreted phosphoprotein 1 205965_at 10.18 1.456 BATF Basic , ATF-like 209800_at 20.56 1.282 KRT16 16 221698_s_at 5.522 1.257 CLEC7A C-type lectin domain family 7, member A 209774_x_at 7.863 1.197 CXCL2 Chemokine (C-X-C motif) ligand 2 233534_at 0.188 0.187 KRTAP3-2 Keratin associated protein 3-2 Functional analysis of genes that have .5-fold changes in either the human or murine system revealed their involvement in cell communication, cytokine– cytokine receptor interaction, calcium signaling, histidine metabolism, complement and coagulation cascades, JAK-STAT signaling, and arachidonic acid metabolism. Those genes are among genes in the murine IL-13–induced esophagealtranscriptome that overlapped with the human EE transcriptome (p , 0.05). DOX, mice treated with Dox for 4 wk; EE, biopsy samples from EE patients; NL, biopsy samples from non-EE patients; NO DOX, untreated mice. The Journal of Immunology 665 Downloaded from

FIGURE 6. Eotaxin production in the lung and esophagus. Protein levels of eotaxin 1 (A) and eotaxin-2 (B) in the esophagus are shown after 1–4 wk of DOX administration. Results were normalized to the esophageal protein content and are expressed as mean 6 SD; p , 0.01 for week 1 and 4 lung and esophageal time points compared with DOX on week 0. The esophageal eosinophil count from IL-13 transgenic mice was compared with IL-13/eotaxin-1 http://www.jimmunol.org/ and IL-13/eotaxin-2 KO mice (C). pp , 0.001 wild-type versus KO. The figures are the summary of three independent experiments with n = 4 for each group per experiment. lung (11), but not in the esophagus according to our current study. amyloid). Consistent with a role for TGF-b and MMP-12 in pro- There were 836 genes modified by $2-fold in the lungs or esoph- moting IL-13-induced esophageal fibrosis, DOX significantly in- agus. Cluster analysis stratified IL-13–induced genes into creased levels of esophageal TGF-b1 and MMP-12 mRNA by 2.0- conserved (clusters 2 and 4) and discordant (clusters 1 and 3) and 2.7-fold as assessed by gene chip analysis (data not shown).

clusters between the lungs and the esophagus (Fig. 11). In cluster These two genes are increased in both the lung and esophagus by guest on September 30, 2021 2, 126 genes increased in both the lung and esophagus by .5-fold (cluster 2 above). In cluster 4, 67 genes decreased in both the lung (Supplemental Table IV). Notably, these gene families are involved and esophagus by .5-fold (Supplemental Table V). Among these in chemotaxis (C3a, CCL6, CCL8, CCL9, and CCL11), cytokine genes were the somatotropin hormone gene family (such as pro- signaling (IL-27Ra, IL-7R, and CSFRs), and other immune and lactin-like protein E) and ion binding protein genes (zinc finger inflammatory functions (chitinase 3, platelet , and serum protein 64 and carbonic anhydrase 3). Cluster 4 also included three

FIGURE 7. Effect of Ddbl-GATA (GATA-1 KO) on IL-13 transgene- induced esophageal tissue remodeling. The esophagi of lung-specific IL-13 transgenic mice and IL-13 transgenic/ GATA-1 KO mice after 4 wk of DOX exposure were stained with anti-MBP (A), H&E (B), trichrome staining (C), and BrDU (D). Morphometric analysis was shown for each of those measure- ments. The figures are the summary of three independent experiments with n = 4 for each group per experiment. 666 IL-13 TRANSGENE-INDUCED EE

Discussion Esophageal eosinophilia is the characteristic finding of human EE but the mechanisms involved in tissue pathology, including the role of eosinophils, remain poorly understood (19). Among environ- mental factors, both food and aeroallergen hypersensitivity have been implicated in the induction of EE, suggesting the involvement of Th2 immunity. Indeed, the Th2 cytokine IL-13 has been shown to be markedly overexpressed in the esophagus of EE patients and to induce eotaxin-3 in esophageal epithelial cells, yet the involvement of IL-13 with other aspects of disease remains uncertain. In this study, inducible expression of IL-13 in the lung resulted in extensive esophageal eosinophilia and tissue remodeling. Although pulmo- nary eosinophilia was also observed, the kinetics of eosinophilia was different between the lung and esophagus. In fact, esophageal eosinophilia peaked around day 10 after DOX induction, which is earlier than the peak of pulmonary eosinophilia after DOX induction. Interestingly, both pulmonary and esophageal eosinophilia returned to near baseline levels 3–4 wk after withdrawal of DOX, suggesting that IL-13–induced eosinophilia is reversible in this animal model, Downloaded from FIGURE 8. Accumulation of IL-13/sIL-13Ra2 complexes. Protein similar to eosinophilia’s reversibility in patients after therapy. levels of blood IL-13/sIL-13Ra2 complex (A) after a time course of In asthma patients, tissue remodeling has an important role in DOX exposure were measured using ELISA. Protein content of esophageal chronic inflammation and is part of the mechanism of airway ob- IL-13/sIL 13Ra2 complex and total sIL-13Ra2 after 4 wk of DOX expo- struction (20). In EE patients, esophageal remodeling, including sure were also measured by the same method (B). The figures are the increased tissue fibrosis and angiogenesis, occurs even in pediatric summary of three independent experiments with n = 4 for each group patients (3); however, the mechanisms that promote these changes http://www.jimmunol.org/ per experiment. remain unclear. Our study establishes that overexpressing pulmo- nary IL-13 induces extensive esophageal tissue remodeling, in- genes involved in sensory perception (tectorin b, sry-box containing cluding increased epithelial thickness, collagen deposition, epithe- gene, and cadherin 23) and two genes involved in (zinc lial cell proliferation, angiogenesis, and esophageal circumference. finger protein of the cerebellum 2 and paired box gene 5). Other The increased esophageal circumference, which is visible to the genes in this cluster included IL-12b, adrenergic receptor a 2c, and naked eye, may be responsible for the esophageal furrowing notable keratin complex 2. In cluster 3, 52 genes decreased in the lung but by endoscopic analysis in patients (21). After lung-specific IL-13 increased in the esophagus (Supplemental Table VI). In cluster 1, 39 transgene induction, a significant accumulation of IL-13 protein was genes increased in the lung but decreased in the esophagus (Supple- observed in both the lung and the esophagus. The content of IL-13 in by guest on September 30, 2021 mental Table VII). Clusters 1 and 3 are particularly interesting be- the lung was much higher than that in the esophagus, consistent with cause these transcriptomes may be associated with tissue-specific the lung-specific IL-13 transgene design. In addition to the function. Taken together, these results indicate that IL-13 induces accumulation of IL-13 protein, both IL-13/IL-13Ra2 complex and a set of shared and tissue-specific genes in the lung and esophagus. total IL-13Ra2 were increased after IL-13 transgene induction.

FIGURE 9. Effect of IL-13Ra2 deficiency on IL-13 transgene-induced esophageal tissue remodeling. The esophagus of lung-specific IL-13 transgenic mice with or without IL-13Ra2 deletion were studied for esophageal eosinophilia (A), epithelial thickness (B), collagen deposition (C), and esophageal circumference (D). The figures are the summary of three independent experiments with n = 4 for each group per experiment. The Journal of Immunology 667

FIGURE 10. Effect of IL-13Ra2 deficiency on death rate and weight loss. The death rate (A) and weight loss (B) were shown for IL-13 transgenic mice with or without IL-13Ra2 deficiency after 4 wk of DOX exposure. B, Clear bars indicate groups without IL-13Ra2 deficiency and dark bars indicate groups with IL-13Ra2 deficiency. The figures are the summary of three independent exper- iments with n = 4 for each group per experiment. Downloaded from http://www.jimmunol.org/

IL-13 mRNA in situ hybridization failed to detect IL-13–positive philia. Notably, murine eotaxin-3 is a pseudogene in mice, and cells in the esophagus of the IL-13–expressing mice (data not mouse eotaxin-1 appears to be the functional homolog of human shown). Perhaps IL-13 protein accumulation in the esophagus eotaxin-3, which is the main chemokine operational in human EE may be derived from swallowing pulmonary-derived IL-13. Free (22, 23). Furthermore, we demonstrated that esophageal remodeling IL-13 that is produced in the lung and either swallowed or carried is eosinophil-independent, inasmuch as we observed the same de- by guest on September 30, 2021 from the lung to the esophagus via the blood likely binds to the type gree of tissue remodeling in eosinophil-sufficient and -deficient 2 IL-4R in the esophagus. The lack of gastric and intestinal eosin- IL-13 transgenic mice. Thus, we have identified an IL-13–driven ophilia distal to the esophagus is more supportive of the swallowing pathway that mediates EE-like changes independent of eosinophils, theory. Regardless, tissue eosinophilia did not occur distal to the suggesting that some aspects of the disease may occur independent esophagus, highlighting the esophageal tissue-specific effect of of eosinophils in humans. In our prior studies, we have demonstrated IL-13, at least in this experimental system. a role of IL-5–driven eosinophils in aeroallergen-induced epithelial In this study, we observed the coexistence of esophageal eosin- proliferation (as measured by BrdU and basal layer thickness) and ophilia and tissue remodeling. Moreover, we demonstrated that collagen layer thickness (5). In contrast, the current study is the first eotaxin-1 (but not eotaxin-2) is required for esophageal eosino- to identify eosinophil-independent responses in EE. Preliminary

FIGURE 11. Esophageal transcript profile of lung-specific IL-13 transgenic mice. Comparison of transcript profiles of CC10-rtTa (tet on)-IL-13 transgenic mice in the lungs and esophagus is shown. The genes (2-fold cutoff) in lungs of mice treated with doxycycline (+, DOX 30 d) or left untreated (2, NO-DOX) were compared with the genes significantly different (p , 0.01) in the esophagus of mice treated with DOX (30 d) or left untreated (NO-DOX). The overlap of the two signatures, composed of 836 genes, is presented in a heat diagram and is clustered using gene tree analysis (standard correlation). Cluster 1 contains genes upregulated (red) in the lung and downregulated (blue) in the esophagus. Cluster 2 contains genes upregulated in the lung and the esophagus. Cluster 3 contains genes downregulated in the lung and upregulated in the esophagus. Cluster 4 contains genes downregulated in the lung and the esophagus. 668 IL-13 TRANSGENE-INDUCED EE studies in humans have suggested that humanized anti–IL-5 is a (Cincinnati Children’s Hospital Medical Center) for kindly providing the potentially useful therapy for lowering esophageal eosinophilia, al- CC10 activator mice. We also thank the Cincinnati Children’s Hospital though an effect on remodeling has not yet been proven; in fact, the Medical Center Pulmonary and Pathology Morphology Core laboratories limited patients examined still have extensive tissue remodeling (22, for their help. 24). We recognize that our system involves supraphysiological levels of IL-13; therefore, the direct action of IL-13 (not requiring eosino- phils) may not apply to an Ag-driven process in patients. Neverthe- Disclosures less, our study provides a rationale for therapeutic intervention M.E.R. is a consultant for several companies. focused on the noneosinophilic components of the disease. Further- more, because IL-13–induced pulmonary remodeling (using the same transgenic system) is eosinophil-dependent (11), whereas, References the remodeling in the esophagus was not, our study highlights dis- 1. Furuta, G. T., C. A. Liacouras, M. H. Collins, S. K. Gupta, C. Justinich, P. E. Putnam, P. Bonis, E. Hassall, A. Straumann, and M. E. Rothenberg; First tinct pathways for disease induction between the lung and esophagus International Gastrointestinal Eosinophil Research Symposium (FIGERS) Sub- even when disease is driven by the same atopic trigger (in this case committees. 2007. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastro- IL-13). Notably, concurrent photomicrographs from the lung of enterology 133: 1342–1363. IL-13 transgenic mice deficient in eosinophils revealed 2. Zuo, L., and M. E. Rothenberg. 2007. Gastrointestinal eosinophilia. Immunol. significantly less remodeling compared with IL-13 transgenic mice Allergy Clin. North Am. 27: 443–455. 3. Aceves, S. S., R. O. Newbury, R. Dohil, J. F. Bastian, and D. H. Broide. 2007. (data not shown). This is consistent with our prior studies (11), which Esophageal remodeling in pediatric eosinophilic esophagitis. J. Allergy Clin. incidentally used experimental lung tissue that overlapped in part Immunol. 119: 206–212. Downloaded from with the exact mice studied in this report. Indeed, transcript 4. Spergel, J., M. E. Rothenberg, and M. Fogg. 2005. Eliminating eosinophilic esophagitis. Clin. Immunol. 115: 131–132. expression profile analysis readily identified shared and unique 5. Mishra, A., S. P. Hogan, E. B. Brandt, and M. E. Rothenberg. 2001. An etio- molecular events between the lung and esophagus. logical role for aeroallergens and eosinophils in experimental esophagitis. J. Clin. Invest. 107: 83–90. To further explore the mechanisms of IL-13–mediated tissue 6. Mishra, A., and M. E. Rothenberg. 2003. Intratracheal IL-13 induces eosino- remodeling, we used a triple transgenic CC10/IL-13/IL-13Ra2 philic esophagitis by an IL-5, eotaxin-1, and STAT6-dependent mechanism. Gastroenterology 125: 1419–1427. deletion mouse model. The triple transgenic mice with IL-13Ra2 http://www.jimmunol.org/ 7. Akei, H. S., A. Mishra, C. Blanchard, and M. E. Rothenberg. 2005. Epicutaneous deletion showed significantly enhanced remodeling including antigen exposure primes for experimental eosinophilic esophagitis in mice. increased esophageal mucosal thickening and collagen deposition Gastroenterology 129: 985–994. as well as clinical features (weight loss and death) compared with 8. Blanchard, C., M. K. Mingler, M. Vicario, J. P. Abonia, Y. Y. Wu, T. X. Lu, M. H. Collins, P. E. Putnam, S. I. Wells, and M. E. Rothenberg. 2007. IL-13 the double transgenic CC10/IL-13 mice. The enhanced esophageal involvement in eosinophilic esophagitis: transcriptome analysis and reversibility remodeling after IL-13Ra2 deletion indicates that IL-13Ra2 with glucocorticoids. J. Allergy Clin. Immunol. 120: 1292–1300. 9. Fulkerson, P. C., C. A. Fischetti, L. M. Hassman, N. M. Nikolaidis, and inhibits IL-13–induced remodeling, consistent with a “decoy” M. E. Rothenberg. 2006. Persistent effects induced by IL-13 in the lung. Am. J. effect of IL-13Ra2 that prevents IL-13 from binding to the stimu- Respir. Cell Mol. Biol. 35: 337–346. latory type 2 IL-4R (17, 25) and with recent pulmonary results from 10. Fichtner-Feigl, S., I. J. Fuss, C. A. Young, T. Watanabe, E. K. Geissler, H. J. Schlitt, A. Kitani, and W. Strober. 2007. Induction of IL-13 triggers by guest on September 30, 2021 IL-13 transgenic IL-13Ra2–deficient mice (26). These findings TGF-beta1-dependent tissue fibrosis in chronic 2,4,6-trinitrobenzene sulfonic indicate that IL-13Ra2–mediated TGF-b–dependent fibrotic effect acid colitis. J. Immunol. 178: 5859–5870. (27) is not likely operational in EE. 11. Fulkerson, P. C., C. A. Fischetti, and M. E. Rothenberg. 2006. Eosinophils and CCR3 regulate interleukin-13 transgene-induced pulmonary remodeling. Am. J. Taken together, our study establishes that (1): pulmonary IL-13 Pathol. 169: 2117–2126. expression induces extensive esophageal tissue eosinophilia and 12. Lee, P. J., X. Zhang, P. Shan, B. Ma, C. G. Lee, R. J. Homer, Z. Zhu, M. Rincon, B. T. Mossman, and J. A. Elias. 2006. ERK1/2 mitogen-activated protein kinase remodeling, including fibrosis, angiogenesis, and epithelial selectively mediates IL-13-induced lung inflammation and remodeling in vivo. J. hyperplasia (2); IL-13 promotes increased esophageal circumfer- Clin. Invest. 116: 163–173. ence (3); esophageal eosinophilia is mediated by eotaxin-1 (and 13. Wan, H., K. H. Kaestner, S. L. Ang, M. Ikegami, F. D. Finkelman, M. T. Stahlman, P. C. Fulkerson, M. E. Rothenberg, and J. A. Whitsett. 2004. Foxa2 regulates not eotaxin-2), which appears to be the functional homolog of alveolarization and goblet cell hyperplasia. Development 131: 953–964. human eotaxin-3, a cytokine considered to have an important role 14. Khodoun, M., C. C. Lewis, J. Q. Yang, T. Orekov, C. Potter, T. Wynn, in human EE (4); tissue remodeling occurs largely independent of M. Mentink-Kane, G. K. Hershey, M. Wills-Karp, and F. D. Finkelman. 2007. Differences in expression, affinity, and function of soluble (s)IL-4Ralpha and eosinophils (5); IL-13Ra2 dampens IL-13–mediated esophageal sIL-13Ralpha2 suggest opposite effects on allergic responses. J. Immunol. 179: pathology and clinical features (6); in vivo, IL-13 induces 6429–6438. 15. Blanchard, C., N. Wang, K. F. Stringer, A. Mishra, P. C. Fulkerson, J. P. Abonia, a marked esophageal transcriptome in mice that overlaps, a least S. C. Jameson, C. Kirby, M. R. Konikoff, M. H. Collins, et al. 2006. in part, with the human EE transcriptome; and (7) IL-13 induces Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic a set of shared genes in the lung and esophagus. Additional trans- esophagitis. J. Clin. Invest. 116: 536–547. 16. Cho, S. J., M. J. Kang, R. J. Homer, H. R. Kang, X. Zhang, P. J. Lee, J. A. Elias, lational studies demonstrated that IL-13 levels directly correlate and C. G. Lee. 2006. Role of early growth response-1 (Egr-1) in interleukin-13- with relevant gene expression in esophageal tissue from EE induced inflammation and remodeling. J. Biol. Chem. 281: 8161–8168. patients. Thus, we establish that IL-13 is sufficient to induce sig- 17. Mentink-Kane, M. M., and T. A. Wynn. 2004. Opposing roles for IL-13 and IL-13 receptor alpha 2 in health and disease. Immunol. Rev. 202: 191–202. nificant esophageal pathology and remodeling in vivo, that this 18. Fichtner-Feigl, S., W. Strober, K. Kawakami, R. K. Puri, and A. Kitani. 2006. process is likely operational in human EE, and that disease pa- IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis. Nat. Med. 12: 99–106. thology of EE occurs largely independent of eosinophils (under 19. Rothenberg, M. E. 2004. Eosinophilic gastrointestinal disorders (EGID). J. Al- these experimental conditions) and is inhibited by IL-13Ra2. lergy Clin. Immunol. 113: 11–28, quiz 29. Consequently, pharmacological targeting of IL-13 production 20. Ward, C., D. P. Johns, R. Bish, M. Pais, D. W. Reid, C. Ingram, B. Feltis, and E. H. Walters. 2001. Reduced airway distensibility, fixed airflow limitation, and and signaling may be a worthwhile pursuit. airway wall remodeling in asthma. Am. J. Respir. Crit. Care Med. 164: 1718–1721. 21. Nurko, S., J. E. Teitelbaum, K. Husain, C. Buonomo, V. L. Fox, D. Antonioli, C. Fortunato, K. Badizadegan, and G. T. Furuta. 2004. Association of Schatzki Acknowledgments ring with eosinophilic esophagitis in children. J. Pediatr. Gastroenterol. Nutr. 38: We thank Drs. Simon Hogan, Anil Mishra, Amal Assa’ad, Margaret Collins, 436–441. Eric Brandt, and Nives Zimmermann for advice and technical assistance, 22. Bullock, J. Z., J. M. Villanueva, C. Blanchard, A. H. Filipovich, P. E. Putnam, M. H. Collins, K. A. Risma, R. M. Akers, C. L. Kirby, B. K. Buckmeier, et al. and Shawna Hottinger for editorial assistance. We thank Dr. James Lee 2007. Interplay of adaptive th2 immunity with eotaxin-3/c-C chemokine receptor (Mayo Clinic) for providing anti-MBP reagent and Dr. Jeffrey Whitsett 3 in eosinophilic esophagitis. J. Pediatr. Gastroenterol. Nutr. 45: 22–31. The Journal of Immunology 669

23. Borchers, M. T., T. Ansay, R. DeSalle, B. L. Daugherty, H. Shen, M. Metzger, receptor a2 regulates the immune and functional response to Nippostrongylus N. A. Lee, and J. J. Lee. 2002. In vitro assessment of chemokine receptor-ligand brasiliensis infection. J. Immunol. 183: 1934–1939. interactions mediating mouse eosinophil migration. J. Leukoc. Biol. 71: 1033–1041. 26. Zheng, T., W. Liu, S. Y. Oh, Z. Zhu, B. Hu, R. J. Homer, L. Cohn, M. J. Grusby, 24. Stein, M. L., M. H. Collins, J. M. Villanueva, J. P. Kushner, P. E. Putnam, and J. A. Elias. 2008. IL-13 receptor alpha2 selectively inhibits IL-13-induced B. K. Buckmeier, A. H. Filipovich, A. H. Assa’ad, and M. E. Rothenberg. 2006. responses in the murine lung. J. Immunol. 180: 522–529. Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. J. Allergy Clin. 27. Fichtner-Feigl, S., C. A. Young, A. Kitani, E. K. Geissler, H. J. Schlitt, and Immunol. 118: 1312–1319. W. Strober. 2008. IL-13 signaling via IL-13R alpha2 induces major downstream 25. Morimoto, M., A. Zhao, R. Sun, J. Stiltz, K. B. Madden, M. Mentink-Kane, fibrogenic factors mediating fibrosis in chronic TNBS colitis. Gastroenterology T. Ramalingam, T. A. Wynn, J. F. Urban, Jr., and T. Shea-Donohue. 2009. IL-13 135: 2003–2013. Downloaded from http://www.jimmunol.org/ by guest on September 30, 2021 experiment. SD. Th as mean± The results areexpressed In (B),BrdU wasusedto analysis. incorporation morphometric 4weeks ofDOXexposurewas st andafter before transgenic mice Supplementary Figure 1:Morphometric analysis

BrdU+ cells/µm basement membrane Epithelial Thickness (µm) 1 1 1 1 2 4 6 8 0 2 4 6 0 0 0 0 0 0 0 ...... 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 2 3 4 5 6 7 A B N N e data are representative of three independent experiments with n= 6 for each group pe withn= 6foreach of threeindependent experiments are representative e data O O D D O O X X ofepithelial thickness and hyperplasia. P=0.01 P=0.002 measure cellular hyperplasia fo hyperplasia measure cellular ained with H&E. The thickness of epithelium wasassessed by ofepithelium thickness The with H&E. ained D O D O X X In (A),theesophagus ofIL-13lung r NO-DOX and DOX groups of mice. r NO-DOX andDOX groupsof mice. r Supplementary Figure 2:Morphometric Analysis independent experiments with n= experiments independent distribution of positive PECAM-1 vessels was analyzed by morphometrics analysis. The data are representative of three and afte before esophaguses IL-13 lungtransgenic mice from 4week andafter before mice esophagus forIL-13 lungtransgenic

Thickness of the trichrome Numbers of Positive Vessels/HPF positive layer (µm) 1 1 2 2 1 1 2 2 3 3 0 5 0 5 0 5 0 5 0 5 0 5 0 5 A B 6 for each group per experiment. Intra-mucosa N O D O X ofcollagen deposition and angiogenesis. P=0.005 r 4weeksof DOX exposure were st r s of DOX exposure is assessed by morphometric analysis. In (B), analysis. assessed bymorphometric is s ofDOX exposure DOX No DOX Intra-epithelium D O X In (A), the trichrome stainingIn (A),thetrichrome of ained with anti-PECAM-1. The The withanti-PECAM-1. ained Affy# Pvalue fold changesymbol gene name 1425295_at 0.035 28.71 Ear11 Eosinophil-associated A family 1418165_at 0.0362 25.43 Itlna Intelectin a 1422317_a_at 0.0259 10.82 Il1rl1 Interleukin 1 receptor-like 1 1424265_at 0.0434 7.978 Npl N-acetylneuraminate pyruvate 1419861_at 0.0248 7.327 Transcribed 1459580_at 0.0113 7.275 G630055G22Rik RIKEN cDNA G630055G22 gene 1426201_at 0.0273 7.154 Igk-V8 Gene model 1499, (NCBI) 1446707_at 0.0303 6.8 Sdccag33 Serologically defined colon antigen 1420118_s_at 0.0373 6.564 Galm Galactose mutarotase 1456994_at 0.0164 5.775 Rassf1 Ras association (RalGDS/AF-6) domain 1439323_a_at 0.0362 5.671 Map4k1 Mitogen activated protein kinase 1 1443552_at 0.00953 5.626 LOC545619 Similar to hypothetical protein LOC57653 1454113_at 0.0368 5.41 4930472D12Rik Mitogen-activated protein kinase 5 1432166_at 0.0124 5.031 E130018N17Rik RIKEN full-length enriched library, clone 1419797_at 0.0469 4.931 AA672641 Expressed sequence AA672641 1427856_a_at 0.0126 4.803 Igk-C Gene model 460, (NCBI) 1459726_at 0.0375 4.751 Ptprn2 RIKEN cDNA 5730406E14 gene 1431271_at 0.0193 4.644 2810428J06Rik 1446970_at 0.038 4.311 Gemin5 Gem (nuclear organelle) associated protein 1454231_a_at 0.0481 4.214 Rpgrip1 Retinitis pigmentosa interacting protein 1 1444353_at 0.0291 4.147 C030040A22Rik Nuclear mitotic apparatus protein 1 1433272_at 0.0246 4.091 A430110A21Rik RIKEN full-length enriched library, clone 1450369_at 0.0286 3.981 Figla Factor in the germline alpha 1449918_at 0.00921 3.957 2310066I10Rik RIKEN cDNA 1810029C22 gene 1457082_at 0.0309 3.806 Ppp1r3f Protein 1 1435131_at 0.0435 3.583 Zfp13 protein 13 1434164_s_at 0.00922 3.443 LOC381251 Expressed sequence AU024076 1446432_at 0.0328 3.361 B530045E10Rik RIKEN cDNA B530045E10 gene 1449805_at 0.0499 3.341 Isp2 Implantation serine 2 1420983_at 0.0024 3.326 Pctp Phosphatidylcholine transfer protein 1440946_at 0.0497 3.272 Adult male medulla oblongata cDNA 1449698_at 0.0106 3.272 C330027C09Rik RIKEN cDNA C330027C09 gene 1421913_at 0.00439 3.162 Mrpl19 Mitochondrial ribosomal protein L19 1445538_at 0.02 3.112 Auts2 Autism susceptibility candidate 2 1438994_at 0.0389 3.111 4933439A12Rik 1452010_at 0.0326 3.086 Chrna3 Cholinergic receptor, alpha polypeptide 3 1426588_at 0.00654 3.029 Tspan10 Tetraspanin 10 1458219_at 0.0396 3.007 Bcas2 Breast carcinoma amplified sequence 2 1431380_at 0.0192 2.897 5730409L17Rik Islet cell autoantigen 1 1448895_a_at 0.0387 2.886 Ctnna2 Catenin (cadherin associated protein) 1440865_at 0.02 2.879 Ifitm6 1427803_at 0.0351 2.877 Pvrl2 Poliovirus receptor-related 2 1447423_at 0.034 2.784 8030451K01Rik RIKEN cDNA 8030451K01 gene 1445687_at 0.0171 2.768 na Gene model 885, (NCBI) 1442823_at 0.0174 2.706 neonate eyeball cDNA 1418061_at 0.0498 2.588 Ltbp2 TGF beta binding protein 2 1418243_at 0.000977 2.583 Fcna Ficolin A 1416965_at 0.0451 2.56 Pcsk1n inhibitor 1430011_at 0.0447 2.55 2610317O13Rik RIKEN cDNA 2610317O13 gene 1458006_at 0.0474 2.526 Cpm Carboxypeptidase M 1418055_at 0.0469 2.506 Neurod4 Neurogenic differentiation 4 1419692_a_at 0.0492 2.504 Ltc4s Leukotriene C4 synthase 1427380_at 0.0233 2.488 Ngfg Nerve growth factor, gamma 1457873_at 0.00792 2.471 11 days embryo gonad cDNA 1438461_at 0.0193 2.415 Khdrbs1 RNA binding, signal transduction associated 1446777_at 0.0479 2.392 Spp2 Secreted phosphoprotein 2 1445279_at 0.045 2.386 Ankrd5 Ankyrin repeat domain 5 1441821_at 0.0374 2.38 NIA Mouse Whole Embryo cDNA Library 1433653_at 0.0391 2.368 BC029169 CDNA sequence BC029169 1439288_at 0.0362 2.354 0710005I19Rik RIKEN cDNA 4930488B01 gene 1450343_at 0.0497 2.331 V1rd1 Vomeronasal 1 receptor, D1 1456829_at 0.0491 2.325 Pnma3 Paraneoplastic antigen MA3 1449216_at 0.0231 2.311 Itgae Integrin, alpha E, epithelial-associated 1447529_at 0.0239 2.292 NIA Mouse cDNA Clone Set 1434779_at 0.0293 2.233 Cbln2 Cerebellin 2 precursor protein 1445768_at 0.00703 2.223 LOC544965 Ankyrin repeat-containing -1 1427374_at 0.0315 2.222 Muc3 Mucin 3, intestinal 1430283_s_at 0.00794 2.215 4930418G15Rik RIKEN cDNA 4930418G15 gene 1437093_at 0.0493 2.175 Dnaic1 RIKEN cDNA 2310040A07 gene 1459571_at 0.0473 2.131 Sh3bgrl SH3-binding glutamic acid-rich protein like 1419482_at 0.0363 2.126 C3ar1 Complement component 3a receptor 1 1422062_at 0.0383 2.123 Msr1 Macrophage scavenger receptor 1 1453956_a_at 0.0241 2.122 Pftk1 PFTAIRE protein kinase 1 1421739_a_at 0.011 2.121 Matk Megakaryocyte-associated tyrosine kinase 1426001_at 0.0182 2.117 Eomes homolog (Xenopus laevis) 1435790_at 0.0419 2.079 Olfm2 RIKEN cDNA 9430006E15 gene 1437787_at 0.0277 2.021 Lrrtm2 Leucine rich transmembrane neuronal 2 1446692_at 0.00938 2.012 1110001M19Rik RIKEN cDNA 1110001M19 gene 1443048_at 0.0421 2.009 Fbxo21 F-box only protein 21 1421864_at 0.0389 2.007 Dbil5 Diazepam binding inhibitor-like 5 Affy number ND vs Dox NL vs EE symbole gene name 207328_at 78.97 21.27 ALOX15 Arachidonate 15-lipoxygenase 204580_at 42.84 7.781 MMP12 12 (macrophage ) 204470_at 21.58 17.41 CXCL1 Chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) 209800_at 20.56 1.282 KRT16 Keratin 16 (focal non-epidermolytic palmoplantar keratoderma) 205965_at 10.18 1.456 BATF Basic leucine zipper transcription factor, ATF-like 209875_s_at 9.593 1.795 SPP1 Secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) 223502_s_at 7.902 2.073 TNFSF13B Tumor necrosis factor (ligand) superfamily, member 13b 209774_x_at 7.863 1.197 CXCL2 Chemokine (C-X-C motif) ligand 2 205681_at 6.3 3.246 BCL2A1 BCL2-related protein A1 206529_x_at 6.125 8.25 SLC26A4 Solute carrier family 26, member 4 207067_s_at 5.76 3.141 HDC Histidine decarboxylase 221698_s_at 5.522 1.257 CLEC7A C-type lectin domain family 7, member A 206172_at 5.426 5.12 IL13RA2 Interleukin 13 receptor, alpha 2 206134_at 5.073 2.853 ADAMDEC1 ADAM-like, decysin 1 205668_at 4.893 2.439 LY75 Lymphocyte antigen 75 203574_at 4.768 2.009 NFIL3 Nuclear factor, interleukin 3 regulated 209125_at 4.579 1.061 KRT6A 205159_at 4.349 3.596 CSF2RB Colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage) 206756_at 4.261 1.763 CHST7 Carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 7 210184_at 4.171 1.415 ITGAX Integrin, alpha X (antigen CD11C (p150), alpha polypeptide) 209301_at 4.088 6.847 CA2 Carbonic anhydrase II 205579_at 4.06 5.666 HRH1 Histamine receptor H1 202803_s_at 4.032 1.52 ITGB2 Integrin, beta 2 (antigen CD18 (p95), lymphocyte function-associated antigen 1; macrophage antigen 1 (mac-1) beta subunit) 210133_at 3.922 1.437 CCL11 Chemokine (C-C motif) ligand 11 201859_at 3.797 3.505 PRG1 Proteoglycan 1, secretory granule 206336_at 3.526 9.173 CXCL6 Chemokine (C-X-C motif) ligand 6 (granulocyte chemotactic protein 2) 209949_at 3.357 2.408 NCF2 Neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) 203854_at 3.346 6.522 IF I factor (complement) 205267_at 3.336 3.472 POU2AF1 POU domain, class 2, associating factor 1 205891_at 3.3 1.324 ADORA2B Adenosine A2b receptor 226218_at 3.112 2.185 IL7R Interleukin 7 receptor 205798_at 3.112 1.164 IL7R Interleukin 7 receptor 209606_at 3.018 2.16 PSCDBP Pleckstrin homology, Sec7 and coiled-coil domains, binding protein 201137_s_at 3.005 1.172 HLA-DPB1 Major histocompatibility complex, class II, DP beta 1 206618_at 2.97 2.122 IL18R1 Interleukin 18 receptor 1 204733_at 2.888 1.739 KLK6 6 (neurosin, zyme) 217767_at 2.88 1.662 C3 Complement component 3 206932_at 2.783 4.522 CH25H Cholesterol 25-hydroxylase 203416_at 2.783 1.908 CD53 CD53 antigen 204122_at 2.741 2.027 TYROBP TYRO protein tyrosine kinase binding protein 203936_s_at 2.732 1.956 MMP9 Matrix metalloproteinase 9 ( B, 92kDa gelatinase, 92kDa type IV ) 207430_s_at 2.715 1.384 MSMB Microseminoprotein, beta- 223541_at 2.713 4.376 HAS3 Decreased expression in renal and prostate 205504_at 2.693 1.939 BTK Bruton agammaglobulinemia tyrosine kinase 202307_s_at 2.657 2.33 TAP1 Transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) 204057_at 2.636 1.272 IRF8 Interferon regulatory factor 8 201666_at 2.622 4.5 TIMP1 Tissue inhibitor of metalloproteinase 1 (erythroid potentiating activity, collagenase inhibitor) 213915_at 2.602 1.355 NKG7 Natural killer cell group 7 sequence 207419_s_at 2.574 1.439 RAC2 Ras-related C3 substrate 2 (rho family, small GTP binding protein Rac2) 202901_x_at 2.494 2.211 CTSS Cathepsin S 210889_s_at 2.463 1.183 FCGR2B Fc fragment of IgG, low affinity IIc, receptor for (CD32) 206761_at 2.45 1.433 CD96 CD96 antigen 207677_s_at 2.411 1.812 NCF4 Neutrophil cytosolic factor 4, 40kDa 206906_at 2.4 1.316 ICAM5 Intercellular adhesion molecule 5, telencephalin 209040_s_at 2.398 2.825 PSMB8 Proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional protease 7) 204961_s_at 2.375 2.054 NCF1 Neutrophil cytosolic factor 1 (47kDa, chronic granulomatous disease, autosomal 1) 205055_at 2.369 1.741 ITGAE Integrin, alpha E (antigen CD103, human mucosal lymphocyte antigen 1; alpha polypeptide) 211048_s_at 2.299 1.232 PDIA4 Protein disulfide family A, member 4 203879_at 2.288 1.55 PIK3CD Phosphoinositide-3-kinase, catalytic, delta polypeptide 213059_at 2.275 1.115 CREB3L1 CAMP responsive element binding protein 3-like 1 205180_s_at 2.261 1.919 ADAM8 A and metalloproteinase domain 8 202655_at 2.26 1.238 ARMET Arginine-rich, mutated in early stage tumors 207387_s_at 2.232 1.125 GK Glycerol kinase 219033_at 2.212 1.972 PARP8 Poly (ADP-ribose) polymerase family, member 8 217478_s_at 2.203 1.444 HLA-DMA Major histocompatibility complex, class II, DM alpha 201641_at 2.201 2.539 BST2 Bone marrow stromal cell antigen 2 204502_at 2.166 1.06 SAMHD1 SAM domain and HD domain 1 219183_s_at 2.16 1.234 PSCD4 Pleckstrin homology, Sec7 and coiled-coil domains 4 204007_at 2.159 1.635 FCGR3B Fc fragment of IgG, low affinity IIIa, receptor (CD16a) 202269_x_at 2.151 1.838 GBP1 Guanylate binding protein 1, interferon-inducible, 67kDa 205101_at 2.145 1.618 MHC2TA MHC class II transactivator 204533_at 2.136 1.056 CXCL10 Chemokine (C-X-C motif) ligand 10 204912_at 2.127 1.554 IL10RA Interleukin 10 receptor, alpha 219885_at 2.124 1.654 FLJ10260 Hypothetical protein FLJ10260 206643_at 2.12 1.569 HAL Histidine ammonia-lyase 210865_at 2.114 1.098 FASLG Fas ligand (TNF superfamily, member 6) 208304_at 2.093 1.356 CCR3 Chemokine (C-C motif) receptor 3 201060_x_at 2.092 2.685 STOM Stomatin 201062_at 2.092 1.218 STOM Stomatin 205167_s_at 2.085 1.311 CDC25C cycle 25C 202842_s_at 2.084 1.019 DNAJB9 DnaJ (Hsp40) homolog, subfamily B, member 9 202638_s_at 2.077 1.858 ICAM1 Intercellular adhesion molecule 1 (CD54), human rhinovirus receptor 225574_at 2.077 1.375 RWDD4A Hypothetical protein MGC10198 210971_s_at 2.055 0.965 ARNTL Homo sapiens aryl hydrocarbon receptor nuclear translocator-like (ARNTL), transcript variant 2, mRNA. 207957_s_at 2.042 1.792 PRKCB1 Protein kinase C, beta 1 202729_s_at 2.027 1.496 LTBP1 Latent transforming growth factor beta binding protein 1 221561_at 1.951 1.551 SOAT1 Sterol O-acyltransferase (acyl-Coenzyme A: cholesterol acyltransferase) 1 203765_at 1.94 1.292 GCA Grancalcin, EF-hand calcium binding protein 203402_at 1.93 1.367 KCNAB2 Potassium voltage-gated channel, shaker-related subfamily, beta member 2 202076_at 1.887 1.245 BIRC2 Baculoviral IAP repeat-containing 2 218223_s_at 1.872 1.224 OC120 CK2 interacting protein 1; HQ0024c protein 209906_at 1.867 1.819 C3AR1 Complement component 3a receptor 1 227402_s_at 1.859 1.227 C8orf53 Hypothetical protein MGC14595 215933_s_at 1.827 1.305 HHEX Hematopoietically expressed 230031_at 1.827 1.105 HSPA5 Heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa) 210128_s_at 1.825 1.155 LTB4R Leukotriene B4 receptor 221325_at 1.823 1.006 KCNK13 Potassium channel, subfamily K, member 13 203927_at 1.793 2.106 NFKBIE Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon 206087_x_at 1.789 1.093 HFE Hemochromatosis 218154_at 1.788 1.528 GSDMDC1 Gasdermin domain containing 1 206332_s_at 1.775 1.73 IFI16 Interferon, gamma-inducible protein 16 225353_s_at 1.773 1.933 C1QG Complement component 1, q subcomponent, gamma polypeptide 218615_s_at 1.773 1.043 TMEM39A Transmembrane protein 39A 214866_at 1.77 1.572 PLAUR , receptor 205270_s_at 1.768 2.004 LCP2 Lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) 204420_at 1.761 1.414 FOSL1 FOS-like antigen 1 203332_s_at 1.751 1.494 INPP5D Inositol polyphosphate-5-phosphatase, 145kDa 223583_at 1.75 1.025 TNFAIP8L2 Tumor necrosis factor, alpha-induced protein 8-like 2 221529_s_at 1.747 1.062 PLVAP Plasmalemma vesicle associated protein 235148_at 1.727 1.441 KRTCAP3 Keratinocyte associated protein 3 206181_at 1.713 1.94 SLAMF1 Signaling lymphocytic activation molecule family member 1 201897_s_at 1.707 1.588 CKS1B CDC28 protein kinase regulatory subunit 1B 207530_s_at 1.698 0.923 CDKN2B Cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) 201743_at 1.682 2.229 CD14 CD14 antigen 206617_s_at 1.676 1.275 RENBP Renin binding protein 223220_s_at 1.666 2.296 PARP9 Poly (ADP-ribose) polymerase family, member 9 202672_s_at 1.664 2.804 ATF3 Homo sapiens activating transcription factor 3 (ATF3), transcript variant 3, mRNA. 207425_s_at 1.655 1.197 9-Sep Septin 9 227458_at 1.654 1.833 PDCD1LG1 CD274 antigen 217716_s_at 1.653 1.176 SEC61A1 Sec61 alpha 1 subunit (S. cerevisiae) 208130_s_at 1.652 1.068 TBXAS1 Thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A) 203213_at 1.644 2.247 CDC2 Cell division cycle 2, G1 to S and G2 to M 204220_at 1.64 1.742 GMFG Glia maturation factor, gamma 221865_at 1.633 1.45 C9orf91 9 open reading frame 91 204549_at 1.627 1.463 IKBKE Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon 203471_s_at 1.626 1.382 PLEK Pleckstrin 223553_s_at 1.615 1.968 DOK3 Docking protein 3 218893_at 1.614 1.202 ISOC2 Isochorismatase domain containing 2 204170_s_at 1.611 1.671 CKS2 CDC28 protein kinase regulatory subunit 2 223209_s_at 1.607 1.122 SELS Selenoprotein S 218232_at 1.605 2.244 C1QA Complement component 1, q subcomponent, alpha polypeptide 218721_s_at 1.596 1.163 C1orf27 40S ribosomal protein S3 (RPS3B) 222986_s_at 1.593 1.82 SCOTIN Scotin 204232_at 1.588 2.21 FCER1G Fc fragment of IgE, high affinity I, receptor for; gamma polypeptide 204357_s_at 1.588 1.322 LIMK1 LIM domain kinase 1 223454_at 1.587 2.371 CXCL16 Chemokine (C-X-C motif) ligand 16 206919_at 1.586 1.077 ELK4 ELK4, ETS-domain protein (SRF accessory protein 1) 209031_at 1.584 3.386 IGSF4 Immunoglobulin superfamily, member 4 202095_s_at 1.58 1.767 BIRC5 Effector cell protease receptor 1 230840_at 1.58 1.075 LOC388588 Hypothetical gene supported by BC035379; BC042129 219506_at 1.579 1.639 C1orf54 open reading frame 54 219041_s_at 1.559 1.375 REPIN1 Replication initiator 1 204955_at 1.538 1.418 SRPX Sushi-repeat-containing protein, X-linked 203508_at 1.538 1.37 TNFRSF1B Tumor necrosis factor receptor superfamily, member 1B 202580_x_at 1.537 1.83 FOXM1 Forkhead box M1 211530_x_at 1.529 1.23 HLA-G HLA-G histocompatibility antigen, class I, G 201954_at 1.527 1.758 ARPC1B Actin related protein 2/3 complex, subunit 1B, 41kDa 203133_at 1.526 1.074 SEC61B Sec61 beta subunit 223325_at 1.519 1.274 TXNDC11 Thioredoxin domain containing 11 221004_s_at 1.517 1.261 ITM2C Integral membrane protein 2C 226942_at 1.51 1.413 PHF20L1 PHD finger protein 20-like 1 201891_s_at 1.51 1.236 B2M Beta-2-microglobulin 203888_at 1.507 1.498 THBD Thrombomodulin 208018_s_at 1.503 1.808 HCK Hemopoietic cell kinase 218870_at 1.492 1.916 ARHGAP15 Rho GTPase activating protein 15 204482_at 1.483 1.345 CLDN5 Claudin 5 (transmembrane protein deleted in velocardiofacial syndrome) 221142_s_at 1.48 1.214 PECR Peroxisomal trans-2-enoyl-CoA reductase 207826_s_at 1.479 2.796 ID3 Inhibitor of DNA binding 3, dominant negative helix-loop-helix protein 202827_s_at 1.479 1.415 MMP14 Matrix metalloproteinase 14 (membrane-inserted) 223299_at 1.477 1.003 SEC11L3 SEC11-like 3 (S. cerevisiae) 223264_at 1.475 1.322 MESDC1 Mesoderm development candidate 1 203418_at 1.474 1.795 CCNA2 Cyclin A2 222639_s_at 1.471 0.945 FLJ22662 Hypothetical protein FLJ22662 212460_at 1.467 0.924 C14orf147 open reading frame 147 200618_at 1.458 1.539 LASP1 LIM and SH3 protein 1 222162_s_at 1.449 2.138 ADAMTS1 A disintegrin-like and metalloprotease (reprolysin type) with type 1 motif, 1 202659_at 1.446 2.452 PSMB10 Proteasome (prosome, macropain) subunit, beta type, 10 200814_at 1.443 1.493 PSME1 Proteasome (prosome, macropain) activator subunit 1 (PA28 alpha) 202531_at 1.441 2.394 IRF1 Interferon regulatory factor 1 205061_s_at 1.441 1.348 EXOSC9 218747_s_at 1.439 1.615 TAPBPL TAP binding protein-like 206214_at 1.434 1.7 PLA2G7 A2, group VII (platelet-activating factor acetylhydrolase, plasma) 203139_at 1.43 1.68 DAPK1 Death-associated protein kinase 1 205479_s_at 1.425 1.763 PLAU Plasminogen activator, urokinase 210993_s_at 1.425 1.393 SMAD1 SMAD, mothers against DPP homolog 1 (Drosophila) 202897_at 1.424 1.846 PTPNS1 Protein tyrosine phosphatase, non-receptor type substrate 1 201785_at 1.418 2.26 RNASE1 Ribonuclease, RNase A family, 1 (pancreatic) 203379_at 1.418 1.457 RPS6KA1 Ribosomal protein S6 kinase, 90kDa, polypeptide 1 224733_at 1.416 1.528 CMTM3 Chemokine-like factor super family 3 203554_x_at 1.412 1.523 PTTG1 Pituitary tumor-transforming 1 207992_s_at 1.409 1.838 AMPD3 Adenosine monophosphate deaminase (isoform E) 204088_at 1.408 1.176 P2RX4 Purinergic receptor P2X, ligand-gated ion channel, 4 226178_at 1.397 1.219 SOCS4 Suppressor of cytokine signaling 4 208674_x_at 1.397 1.069 DDOST Dolichyl-diphosphooligosaccharide-protein glycosyltransferase 220532_s_at 1.394 2.852 LR8 LR8 protein 206687_s_at 1.393 1.732 PTPN6 Protein tyrosine phosphatase, non-receptor type 6 218082_s_at 1.389 1.423 UBP1 Upstream binding protein 1 (LBP-1a) 219179_at 1.389 1.206 DACT1 Dapper, antagonist of beta-catenin, homolog 1 (Xenopus laevis) 209239_at 1.378 1.268 NFKB1 Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) 202953_at 1.368 2.662 C1QB Complement component 1, q subcomponent, beta polypeptide 201011_at 1.363 1.195 RPN1 Hypothetical protein FLJ40473 226076_s_at 1.36 1.506 MBD6 Methyl-CpG binding domain protein 6 203981_s_at 1.349 1.37 ABCD4 ATP-binding cassette, sub-family D (ALD), member 4 211339_s_at 1.325 1.644 ITK IL2-inducible T-cell kinase 217992_s_at 1.315 1.901 EFHD2 EF-hand domain family, member D2 207134_x_at 1.313 7.732 TPSB2 Tryptase beta 2 202815_s_at 1.312 1.354 HEXIM1 Hexamethylene bis-acetamide inducible 1 201465_s_at 1.288 1.007 JUN V-jun sarcoma virus 17 oncogene homolog (avian) 218308_at 1.279 1.836 TACC3 Transforming, acidic coiled-coil containing protein 3 202180_s_at 1.276 1.869 MVP Major vault protein 204255_s_at 1.274 2.086 VDR Vitamin D (1,25- dihydroxyvitamin D3) receptor 201762_s_at 1.274 1.63 PSME2 Proteasome (prosome, macropain) activator subunit 2 (PA28 beta) 216248_s_at 1.272 1.964 NR4A2 subfamily 4, group A, member 2 218920_at 1.272 1.067 FLJ10404 Hypothetical protein FLJ10404 215380_s_at 1.27 0.921 C7orf24 Chromosome 7 open reading frame 24 219787_s_at 1.259 1.993 ECT2 Epithelial cell transforming sequence 2 oncogene 214032_at 1.259 1.592 ZAP70 Zeta-chain (TCR) associated protein kinase 70kDa 202520_s_at 1.254 1.167 MLH1 MutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) 211012_s_at 1.253 1.401 PML Promyelocytic leukemia 219063_at 1.251 1.012 C1orf35 Chromosome 1 open reading frame 35 207181_s_at 1.249 2.651 CASP7 Caspase 7, apoptosis-related cysteine protease 209509_s_at 1.234 1.132 DPAGT1 Dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1 (GlcNAc-1-P ) 201159_s_at 1.233 1.121 NMT1 N-myristoyltransferase 1 217168_s_at 1.231 0.999 HERPUD1 Homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1 211881_x_at 1.23 1.286 IGLC2 Immunoglobulin lambda joining 3 230174_at 1.226 1.143 LYPLAL1 -like 1 202910_s_at 1.222 1.721 CD97 CD97 antigen 200670_at 1.218 1.204 XBP1 X-box binding protein 1 222140_s_at 1.201 1.183 GPR89 G protein-coupled receptor 89 220642_x_at 1.201 1.024 GPR89 G protein-coupled receptor 89 228714_at 1.2 1.087 PRKRA Protein kinase, interferon-inducible double stranded RNA dependent activator 209139_s_at 1.2 0.992 PRKRA Protein kinase, interferon-inducible double stranded RNA dependent activator 201174_s_at 1.197 1.167 TERF2IP Telomeric repeat binding factor 2, interacting protein 211762_s_at 1.196 1.64 KPNA2 alpha 2 (RAG cohort 1, alpha 1) 200706_s_at 1.189 3.332 LITAF Lipopolysaccharide-induced TNF factor 222464_s_at 1.189 1.203 C10orf119 open reading frame 119 204319_s_at 1.187 0.995 RGS10 Regulator of G-protein signalling 10 202348_s_at 1.185 1.286 TOR1A Torsin family 1, member A (torsin A) 204462_s_at 1.184 2.266 SLC16A2 Solute carrier family 16 (monocarboxylic acid transporters), member 2 219368_at 1.184 0.579 NAP1L2 Nucleosome assembly protein 1-like 2 202871_at 1.176 1.795 TRAF4 TNF receptor-associated factor 4 209408_at 1.16 1.54 KIF2C Kinesin family member 2C 201997_s_at 1.16 1.448 SPEN Spen homolog, transcriptional regulator (Drosophila) 237094_at 1.155 1.03 FAM19A5 Family with sequence similarity 19 (chemokine (C-C motif)-like), member A5 201005_at 1.153 1.575 CD9 CD9 antigen (p24) 209950_s_at 1.15 1.546 VILL Villin-like 202876_s_at 1.145 1.341 PBX2 Pre-B-cell leukemia transcription factor 2 235175_at 1.14 1.843 GBP4 Guanylate binding protein 4 234295_at 1.139 1.599 DBR1 Debranching homolog 1 (S. cerevisiae) 201892_s_at 1.132 1.085 IMPDH2 IMP (inosine monophosphate) dehydrogenase 2 200839_s_at 1.132 1.043 CTSB Cathepsin B 226544_x_at 1.127 1.262 MUTED Thioredoxin domain containing 5 218086_at 1.124 1.066 NPDC1 Neural proliferation, differentiation and control, 1 207741_x_at 1.118 3.561 TPSB2 Tryptase beta 2 201422_at 1.114 2.493 IFI30 Interferon, gamma-inducible protein 30 218916_at 1.111 1.226 FLJ23436 Hypothetical protein FLJ23436 226008_at 1.11 1.209 NDNL2 Necdin-like 2 201995_at 1.105 1.684 EXT1 Exostoses (multiple) 1 200053_at 1.1 1.267 SPAG7 Sperm associated antigen 7 208361_s_at 1.097 1.362 POLR3D Polymerase (RNA) III (DNA directed) polypeptide D, 44kDa 204150_at 1.096 2.08 STAB1 Stabilin 1 223620_at 1.093 2.216 GPR34 221011_s_at 1.087 3.057 LBH Likely ortholog of mouse limb-bud and gene 202381_at 1.086 1.515 ADAM9 A disintegrin and metalloproteinase domain 9 (meltrin gamma) 201765_s_at 1.067 1.454 HEXA Hexosaminidase A (alpha polypeptide) 203744_at 1.058 1.6 HMGB3 Homo sapiens high-mobility group box 3 (HMGB3), mRNA. 208659_at 1.055 1.449 CLIC1 Chloride intracellular channel 1 223028_s_at 1.047 0.303 SNX9 Sorting nexin 9 201953_at 1.045 1.584 CIB1 Calcium and integrin binding 1 (calmyrin) 223164_at 1.042 1.543 CCM2 Cerebral cavernous malformation 2 201189_s_at 1.028 1.756 ITPR3 Inositol 1,4,5-triphosphate receptor, type 3 201889_at 1.018 1.736 FAM3C Family with sequence similarity 3, member C 213800_at 1.015 2.846 CFH Complement factor H 200901_s_at 1.013 1.429 M6PR Mannose-6-phosphate receptor (cation dependent) 201576_s_at 1.009 1.577 GLB1 Galactosidase, beta 1 204240_s_at 1.008 2.003 SMC2L1 SMC2 structural maintenance of 2-like 1 (yeast) 221042_s_at 1.003 2.386 CLMN Calmin (calponin-like, transmembrane) 203978_at 0.996 1.387 NUBP1 Nucleotide binding protein 1 (MinD homolog, E. coli) 201949_x_at 0.987 0.797 CAPZB Capping protein (actin filament) muscle Z-line, beta 209163_at 0.977 0.664 CYB561 Cytochrome b-561 210542_s_at 0.953 1.684 SLCO3A1 Solute carrier organic anion transporter family, member 3A1 208792_s_at 0.946 2.685 CLU Clusterin (complement lysis inhibitor, SP-40,40, sulfated glycoprotein 2, testosterone-repressed prostate message 2, apolipoprotein J) 203502_at 0.943 0.435 BPGM 2,3-bisphosphoglycerate mutase 209944_at 0.939 0.858 ZNF410 Zinc finger protein 410 238740_at 0.921 0.967 MGC2744 Hypothetical protein MGC2744 202187_s_at 0.917 0.787 PPP2R5A 2, regulatory subunit B (B56), alpha isoform 211055_s_at 0.915 0.69 INVS Inversin 209998_at 0.913 1.535 PIGO Phosphatidylinositol glycan, class O 201832_s_at 0.908 0.7 VDP Vesicle docking protein p115 223625_at 0.908 0.571 DRCTNNB1A Down-regulated by Ctnnb1, a 233836_at 0.907 0.804 TNRC6A Trinucleotide repeat containing 6A 218434_s_at 0.9 0.792 AACS Acetoacetyl-CoA synthetase 211433_x_at 0.898 0.721 KIAA1539 KIAA1539 218254_s_at 0.882 0.763 SAR1B 217943_s_at 0.878 2.043 RPRC1 Arginine/proline rich coiled-coil 1 201735_s_at 0.869 0.573 CLCN3 Chloride channel 3 203081_at 0.868 0.754 CTNNBIP1 Catenin, beta interacting protein 1 202742_s_at 0.868 0.495 PRKACB Protein kinase, cAMP-dependent, catalytic, beta 218739_at 0.865 0.425 ABHD5 Abhydrolase domain containing 5 200738_s_at 0.861 0.885 PGK1 Phosphoglycerate kinase 1 201899_s_at 0.835 0.918 UBE2A Ubiquitin-conjugating enzyme E2A (RAD6 homolog) 206216_at 0.834 1.002 STK23 Serine/threonine kinase 23 227276_at 0.827 0.512 PLXDC2 Plexin domain containing 2 208606_s_at 0.825 0.607 WNT4 Wingless-type MMTV integration site family, member 4 218990_s_at 0.823 0.878 SPRR3 Small proline-rich protein 3 203853_s_at 0.819 0.661 GAB2 GRB2-associated binding protein 2 206085_s_at 0.817 0.678 CTH Cystathionase (cystathionine gamma-lyase) 217127_at 0.817 0.389 CTH Cystathionase (cystathionine gamma-lyase) 208832_at 0.815 0.794 ATXN10 Ataxin 10 205670_at 0.81 0.851 GAL3ST1 Galactose-3-O-sulfotransferase 1 207980_s_at 0.808 0.277 CITED2 Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2 217938_s_at 0.807 0.821 KCMF1 Potassium channel modulatory factor 1 202917_s_at 0.803 0.897 S100A8 S100 calcium binding protein A8 (calgranulin A) 239078_at 0.799 0.618 C1orf58 Chromosome 1 open reading frame 58 202166_s_at 0.796 0.609 PPP1R2 , regulatory (inhibitor) subunit 2 204888_s_at 0.786 0.869 NEURL Neuralized-like (Drosophila) 207808_s_at 0.781 0.706 PROS1 Protein S (alpha) 202893_at 0.779 0.605 UNC13B Unc-13 homolog B (C. elegans) 218417_s_at 0.774 0.787 FLJ20489 Hypothetical protein FLJ20489 218225_at 0.773 1.414 SITPEC Signaling intermediate in Toll pathway, evolutionarily conserved 202455_at 0.767 0.654 HDAC5 Histone deacetylase 5 202154_x_at 0.759 0.745 TUBB3 Tubulin, beta 3 213476_x_at 0.759 0.657 TUBB3 Tubulin, beta 3 218666_s_at 0.753 0.684 STX17 Syntaxin 17 203303_at 0.75 0.774 DYNLT3 T-complex-associated-testis-expressed 1-like 213552_at 0.75 0.706 GLCE Glucuronyl C5-epimerase 243550_at 0.749 0.623 ZDHHC21 Zinc finger, DHHC-type containing 21 218059_at 0.747 0.835 LOC51123 HSPC038 protein 203585_at 0.747 0.662 ZNF185 Zinc finger protein 185 (LIM domain) 202282_at 0.742 0.772 HADH2 Hydroxyacyl-Coenzyme A dehydrogenase, type II 203430_at 0.739 0.761 HEBP2 Heme binding protein 2 225268_at 0.736 0.692 KPNA4 Karyopherin alpha 4 (importin alpha 3) 209378_s_at 0.726 0.687 KIAA1128 KIAA1128 233730_at 0.725 0.765 KIAA1411 KIAA1411 225154_at 0.724 0.606 SYAP1 associated protein 1, SAP47 homolog (Drosophila) 225088_at 0.721 0.491 FLJ31153 Hypothetical protein FLJ31153 202960_s_at 0.72 0.855 MUT Methylmalonyl Coenzyme A mutase 221606_s_at 0.701 0.806 NSBP1 Nucleosomal binding protein 1 229534_at 0.697 0.446 ACOT4 Peroxisomal acyl-CoA 2B 225631_at 0.695 0.651 KIAA1706 KIAA1706 protein 218111_s_at 0.689 0.586 CMAS Cytidine monophosphate N-acetylneuraminic acid synthetase 209365_s_at 0.686 0.469 ECM1 protein 1 206044_s_at 0.685 0.697 BRAF V-raf murine sarcoma viral oncogene homolog B1 220753_s_at 0.682 0.667 CRYL1 Crystallin, lambda 1 244212_at 0.679 0.87 CCNC Cyclin C 219793_at 0.678 0.408 SNX16 Sorting nexin 16 206419_at 0.659 0.801 RORC RAR-related orphan receptor C 236534_at 0.649 0.57 BNIPL BCL2/adenovirus E1B 19kD interacting protein like 202805_s_at 0.633 0.655 ABCC1 ATP-binding cassette, sub-family C (CFTR/MRP), member 1 201699_at 0.631 0.747 PSMC6 Proteasome (prosome, macropain) 26S subunit, ATPase, 6 206884_s_at 0.631 0.614 SCEL Sciellin 209142_s_at 0.629 0.527 UBE2G1 Ubiquitin-conjugating enzyme E2G 1 (UBC7 homolog, C. elegans) 235117_at 0.625 0.511 CHAC2 Similar to RIKEN cDNA 2510006C20 gene 209456_s_at 0.621 0.731 FBXW11 F-box and WD-40 domain protein 11 206472_s_at 0.615 0.766 TLE3 Transducin-like enhancer of split 3 (E(sp1) homolog, Drosophila) 32088_at 0.612 0.735 BLZF1 Basic leucine zipper nuclear factor 1 (JEM-1) 221003_s_at 0.609 0.696 CAB39L Calcium binding protein 39-like 216303_s_at 0.607 0.665 MTMR1 Myotubularin related protein 1 228825_at 0.603 0.387 LTB4DH Leukotriene B4 12-hydroxydehydrogenase 205019_s_at 0.593 0.573 VIPR1 Vasoactive intestinal peptide receptor 1 202275_at 0.583 0.752 G6PD Glucose-6-phosphate dehydrogenase 201341_at 0.583 0.507 ENC1 Ectodermal-neural cortex (with BTB-like domain) 220800_s_at 0.576 0.467 TMOD3 Tropomodulin 3 (ubiquitous) 207198_s_at 0.575 0.917 LIMS1 LIM and senescent cell antigen-like domains 1 205014_at 0.574 0.774 FGFBP1 Fibroblast growth factor binding protein 1 242062_at 0.569 0.66 SAMD8 Sterile alpha motif domain containing 8 203407_at 0.557 0.739 PPL Periplakin 222859_s_at 0.547 0.817 DAPP1 Dual adaptor of phosphotyrosine and 3-phosphoinositides 223612_s_at 0.546 0.844 LNX1 Ligand of numb-protein X 223611_s_at 0.546 0.468 LNX1 Ligand of numb-protein X 218180_s_at 0.545 0.634 EPS8L2 EPS8-like 2 223145_s_at 0.535 0.741 C6orf166 Chromosome 6 open reading frame 166 210479_s_at 0.522 0.365 RORA RAR-related orphan receptor A 205767_at 0.512 0.699 EREG Epiregulin 209605_at 0.506 0.764 TST Thiosulfate sulfurtransferase (rhodanese) 203665_at 0.501 0.618 HMOX1 Heme oxygenase (decycling) 1 207324_s_at 0.461 0.768 DSC1 Desmocollin 1 215945_s_at 0.461 0.586 TRIM2 Tripartite motif-containing 2 205364_at 0.448 0.653 ACOX2 Acyl-Coenzyme A oxidase 2, branched chain 238702_at 0.44 0.696 ADMP Likely ortholog of androgen down regulated gene expressed in mouse prostate 210868_s_at 0.432 0.566 ELOVL6 ELOVL family member 6, elongation of long chain fatty acids (FEN1/Elo2, SUR4/Elo3-like, yeast) 231875_at 0.416 0.353 KIF21A Kinesin family member 21A 206412_at 0.402 0.626 FER Fer (fps/fes related) tyrosine kinase (phosphoprotein NCP94) 223739_at 0.396 0.216 PADI1 Peptidyl arginine deiminase, type I 210505_at 0.379 0.583 ADH7 Alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide 207146_at 0.379 0.568 KRTHA2 Keratin, hair, acidic, 2 233534_at 0.188 0.187 KRTAP3-2 Keratin associated protein 3-2 Affy # r symbol gene 227833_s_at 0.7 MBD6 Methyl-CpG binding domain protein 6 202422_s_at 0.701 ACSL4 Acyl-CoA synthetase long-chain family member 4 226353_at 0.701 SPPL2A Signal peptide peptidase-like 2A 239294_at 0.701 Transcribed locus 240354_at 0.701 MGC35033 Hypothetical protein MGC35033 227443_at 0.702 C9orf150 Chromosome 9 open reading frame 150 232617_at 0.702 CTSS Cathepsin S 206912_at 0.702 FOXE1 Forkhead box E1 (thyroid transcription factor 2) 226782_at 0.702 SLC25A30 Solute carrier family 25, member 30 209380_s_at 0.702 ABCC5 ATP-binding cassette, sub-family C (CFTR/MRP), member 5 239155_at 0.702 CXADR Coxsackie virus and adenovirus receptor 220180_at 0.702 SE57-1 CTCL tumor antigen se57-1 202688_at 0.702 TNFSF10 Tumor necrosis factor (ligand) superfamily, member 10 205488_at 0.703 GZMA A 205011_at 0.703 LOH11CR2A Loss of heterozygosity, 11, chromosomal region 2, gene A 219405_at 0.703 TRIM68 Tripartite motif-containing 68 206324_s_at 0.703 DAPK2 Death-associated protein kinase 2 204834_at 0.703 FGL2 Fibrinogen-like 2 233813_at 0.703 PPP1R16B; TIMAP; ANKRD4Homo sapiens cDNA: FLJ23247 fis, clone COL03425. 237183_at 0.704 GALNT5 UDP-N-acetyl-alpha-D-galactosamine 204220_at 0.704 GMFG Glia maturation factor, gamma 225732_at 0.704 KLHDC5 Kelch domain containing 5 225545_at 0.704 EEF2K Eukaryotic elongation factor-2 kinase 217456_x_at 0.704 HLA-E Major histocompatibility complex, class I, E 204754_at 0.704 HLF Hepatic leukemia factor 226601_at 0.704 SLC30A7 Solute carrier family 30 (zinc transporter), member 7 205681_at 0.704 BCL2A1 BCL2-related protein A1 238429_at 0.704 TMEM71 Hypothetical protein FLJ33069 1552365_at 0.705 SCIN Scinderin 212944_at 0.705 SLC5A3 Solute carrier family 5 (inositol transporters), member 3 223423_at 0.705 GPR160 G protein-coupled receptor 160 208771_s_at 0.705 LTA4H Leukotriene A4 211906_s_at 0.705 SERPINB4 Serine (or cysteine) proteinase inhibitor, clade B (ovalbumin) 212592_at 0.705 IGJ Immunoglobulin J polypeptide 209930_s_at 0.705 NFE2 Nuclear factor (erythroid-derived 2), 45kDa 200759_x_at 0.705 NFE2L1 Nuclear factor (erythroid-derived 2)-like 1 201739_at 0.705 SGK Serum/glucocorticoid regulated kinase 1554453_at 0.706 HNRPLL Heterogeneous nuclear ribonucleoprotein L-like 202307_s_at 0.706 TAP1 Transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) 213375_s_at 0.706 CG018 Hypothetical gene CG018 229937_x_at 0.706 LILRB1 Leukocyte immunoglobulin-like receptor, subfamily B 223430_at 0.706 SNF1LK2 SNF1-like kinase 2 205781_at 0.706 C16orf7 open reading frame 7 224747_at 0.706 UBE2Q2 Hypothetical protein LOC92912 212829_at 0.706 CDNA FLJ13267 fis, clone OVARC1000964 226576_at 0.707 ARHGAP26 Rho GTPase activating protein 26 238018_at 0.707 LOC285016; PRO1097; RGPsynonyms: PRO1097, RGPG542 205548_s_at 0.707 BTG3 BTG family, member 3 205624_at 0.707 CPA3 Carboxypeptidase A3 (mast cell) 230788_at 0.707 GCNT2 Glucosaminyl (N-acetyl) transferase 2, I-branching enzyme 204068_at 0.707 STK3 Serine/threonine kinase 3 (STE20 homolog, yeast) 226757_at 0.708 IFIT2 Interferon-induced protein with tetratricopeptide repeats 2 235768_at 0.708 SH3RF2 SH3 domain containing ring finger 2 221641_s_at 0.708 ACOT9 207386_at 0.708 CYP7B1 Cytochrome P450, family 7, subfamily B, polypeptide 1 201681_s_at 0.708 DLG5 Discs, large homolog 5 (Drosophila) 223158_s_at 0.708 NEK6 NIMA (never in mitosis gene a)-related kinase 6 213082_s_at 0.708 SLC35D2 Solute carrier family 35, member D2 229699_at 0.708 CDNA FLJ45384 fis, clone BRHIP3021987 225171_at 0.709 ARHGAP18 Rho GTPase activating protein 18 232165_at 0.709 EPPK1 Epiplakin 1 207375_s_at 0.709 IL15RA Interleukin 15 receptor, alpha 226538_at 0.709 MAN2A1 Mannosidase, alpha, class 2A, member 1 201786_s_at 0.709 ADAR Adenosine deaminase, RNA-specific 228442_at 0.709 NFATC2 Nuclear factor of activated T-cells 228700_at 0.71 CXorf38 Chromosome X open reading frame 38 223386_at 0.71 FLJ21103 Hypothetical protein FLJ21103 231399_at 0.71 602977386F1 NIH_MGC_12 Homo sapiens cDNA clone 206082_at 0.71 HCP5 HLA complex P5 225457_s_at 0.711 SEC6L1 SEC6-like 1 (S. cerevisiae) 208438_s_at 0.711 FGR Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homo 227274_at 0.711 KAI1 CD82 antigen 207430_s_at 0.711 MSMB Microseminoprotein, beta- 1559477_s_a 0.712 MEIS1 Meis1, myeloid ecotropic viral integration site 1 homolog (mo 203797_at 0.712 VSNL1 Visinin-like 1 204781_s_at 0.712 FAS Fas (TNF receptor superfamily, member 6) 1552807_a_a 0.713 SIGLEC10 Sialic acid binding Ig-like lectin 10 210664_s_at 0.713 TFPI 200973_s_at 0.713 TSPAN3 Tetraspanin 3 209120_at 0.713 NR2F2 Nuclear receptor subfamily 2, group F, member 2 214459_x_at 0.714 HLA-C Major histocompatibility complex, class I, C 219947_at 0.714 CLEC4A C-type lectin domain family 4, member A 201487_at 0.714 CTSC Cathepsin C 201328_at 0.714 ETS2 V-ets erythroblastosis virus E26 oncogene homolog 2 (avian) 208914_at 0.714 GGA2 Golgi associated, gamma adaptin ear containing, ARF binding protei 206332_s_at 0.714 IFI16 Interferon, gamma-inducible protein 16 218684_at 0.714 LRRC8D Leucine rich repeat containing 8 family, member D 239035_at 0.714 MTHFR 5,10-methylenetetrahydrofolate reductase (NADPH) 205273_s_at 0.714 PITRM1 metalloproteinase 1 204254_s_at 0.714 VDR Vitamin D (1,25- dihydroxyvitamin D3) receptor 227116_at 0.714 HSRG1 MON1 homolog B (yeast) 232422_at 0.715 LOC87769 Hypothetical protein BC004360 241681_at 0.715 RAFTLIN Raft-linking protein 220980_s_at 0.716 ADPGK ADP-dependent glucokinase 206336_at 0.716 CXCL6 Chemokine (C-X-C motif) ligand 6 227475_at 0.716 FOXQ1 Forkhead box Q1 225776_at 0.716 BAZ2A Bromodomain adjacent to zinc finger domain, 2A 226363_at 0.716 ABCC5 ATP-binding cassette, sub-family C (CFTR/MRP), member 5 205269_at 0.716 LCP2 Lymphocyte cytosolic protein 2 203741_s_at 0.717 ADCY7 Adenylate cyclase 7 223638_at 0.717 AE2 Hypothetical protein AE2 201278_at 0.717 DAB2 Disabled homolog 2, mitogen-responsive phosphoprotein 219322_s_at 0.717 WDR8 WD repeat domain 8 203560_at 0.717 GGH Gamma-glutamyl hydrolase 204753_s_at 0.718 HLF Hepatic leukemia factor 223301_s_at 0.718 FLJ23518 HSPC048 protein 231832_at 0.719 GALNT4 UDP-N-acetyl-alpha-D-galactosamine 209815_at 0.719 PTCH Patched homolog (Drosophila) 216231_s_at 0.719 B2M Beta-2-microglobulin 203889_at 0.72 SGNE1 Secretory granule, neuroendocrine protein 1 (7B2 protein) 232277_at 0.72 SLC28A3 Solute carrier family 28 215388_s_at 0.72 CFHL1 Complement factor H-related 1 pseudogene 220048_at 0.72 EDAR Ectodysplasin A receptor 223961_s_at 0.72 CISH Cytokine inducible SH2-containing protein 209688_s_at 0.721 FLJ10996 synonym: MGC13033 219684_at 0.721 IFRG28 28kD interferon responsive protein 1558234_at 0.721 LOC400617 Hypothetical gene supported by AK093963 224412_s_at 0.721 TRPM6 Transient receptor potential cation channel, subfamily M 209795_at 0.721 CD69 CD69 antigen (p60, early T-cell activation antigen) 213800_at 0.721 CFH Complement factor H 225415_at 0.721 DTX3L Deltex 3-like (Drosophila) 201858_s_at 0.721 PRG1 Proteoglycan 1, secretory granule 210314_x_at 0.721 TNFSF13 Tumor necrosis factor (ligand) superfamily, member 12 209546_s_at 0.721 APOL1 Apolipoprotein L, 1 225465_at 0.721 MAGI1 203510_at 0.721 MET Met proto-oncogene (hepatocyte growth factor receptor) 227438_at 0.722 ALPK1 Alpha-kinase 1 228479_at 0.722 Transcribed locus 218383_at 0.722 C14orf94 Chromosome 14 open reading frame 94 205857_at 0.722 SLC18A2 Solute carrier family 18 (vesicular monoamine), member 2 201814_at 0.722 TBC1D5 TBC1 domain family, member 5 208943_s_at 0.722 TLOC1 Translocation protein 1 203798_s_at 0.722 VSNL1 Visinin-like 1 229391_s_at 0.723 LOC441168 Hypothetical protein LOC441168 202086_at 0.723 MX1 Myxovirus resistance 1, interferon-inducible protein 230069_at 0.723 SFXN1 Sideroflexin 1 224701_at 0.723 PARP14 Poly (ADP-ribose) polymerase family, member 14 242057_at 0.723 Transcribed locus 219512_at 0.724 C20orf172 Chromosome 20 open reading frame 172 210218_s_at 0.724 SP100 Nuclear antigen Sp100 209143_s_at 0.725 CLNS1A Chloride channel, nucleotide-sensitive, 1A 202743_at 0.725 PIK3R3 Phosphoinositide-3-kinase, regulatory subunit 3 (p55, gamma 225968_at 0.725 PRICKLE2 Prickle-like 2 (Drosophila) 227334_at 0.725 USP54 Ubiquitin specific protease 54 243585_at 0.725 226600_at 0.725 SMILE SMILE protein 228812_at 0.725 UI-E-EJ0-aho-i-15-0-UI.r1 UI-E-EJ0 Homo sapiens cDNA clon 227396_at 0.726 HM13 Histocompatibility (minor) 13 204157_s_at 0.726 KIAA0999 KIAA0999 protein 230599_at 0.726 RNF19 Ring finger protein 19 206765_at 0.726 KCNJ2 Potassium inwardly-rectifying channel, subfamily J, member 2 213116_at 0.727 NEK3 NIMA (never in mitosis gene a)-related kinase 3 206726_at 0.727 PGDS Prostaglandin D2 synthase, hematopoietic 218986_s_at 0.727 FLJ20035 Hypothetical protein FLJ20035 200905_x_at 0.728 HLA-E Major histocompatibility complex, class I, E 226021_at 0.728 RDH10 Retinol dehydrogenase 10 (all-trans) 202796_at 0.728 SYNPO Synaptopodin 213258_at 0.728 TFPI Tissue factor pathway inhibitor 213790_at 0.728 ADAM12 A disintegrin and metalloproteinase domain 12 (meltrin alpha 64408_s_at 0.728 CALML4 210367_s_at 0.728 PTGES Prostaglandin E synthase 212111_at 0.728 STX12 Syntaxin 12 201061_s_at 0.729 STOM Stomatin 222492_at 0.729 PDXK Pyridoxal (pyridoxine, vitamin B6) kinase 217762_s_at 0.729 RAB31 RAB31, member RAS oncogene family 219033_at 0.73 PARP8 Poly (ADP-ribose) polymerase family, member 8 213293_s_at 0.73 TRIM22 Tripartite motif-containing 22 204489_s_at 0.73 CD44 CD44 antigen (homing function and Indian blood group syste 200878_at 0.73 EPAS1 Endothelial PAS domain protein 1 204780_s_at 0.73 FAS Fas (TNF receptor superfamily, member 6) 226621_at 0.731 FGG Fibrinogen gamma chain 229566_at 0.731 LOC440449 Hypothetical gene supported by AF086204 218815_s_at 0.731 TMEM51 Transmembrane protein 51 203024_s_at 0.731 C5orf15 Chromosome 5 open reading frame 15 217798_at 0.731 CNOT2 CCR4-NOT transcription complex, subunit 2 221059_s_at 0.731 COTL1 Coactosin-like 1 (Dictyostelium) 203854_at 0.731 IF I factor (complement) 217858_s_at 0.732 ARMCX3 Armadillo repeat containing, X-linked 3 219528_s_at 0.732 BCL11B B-cell CLL/lymphoma 11B (zinc finger protein) 213134_x_at 0.732 BTG3 BTG family, member 3 243582_at 0.732 SH3RF2 SH3 domain containing ring finger 2 223377_x_at 0.732 CISH Cytokine inducible SH2-containing protein 204806_x_at 0.732 HLA-F Major histocompatibility complex, class I, F 238668_at 0.732 Transcribed locus, weakly similar to XP_517655.1 PREDICTED 223502_s_at 0.733 TNFSF13B Tumor necrosis factor (ligand) superfamily, member 13b 209140_x_at 0.733 HLA-B Major histocompatibility complex, class I, B 205579_at 0.733 HRH1 Histamine receptor H1 230464_at 0.734 EDG8 Endothelial differentiation, sphingolipid G-protein-coupled rec 202531_at 0.734 IRF1 Interferon regulatory factor 1 222258_s_at 0.734 SH3BP4 SH3-domain binding protein 4 221900_at 0.734 COL8A2 Collagen, type VIII, alpha 2 203474_at 0.734 IQGAP2 IQ motif containing GTPase 206529_x_at 0.734 SLC26A4 Solute carrier family 26, member 4 225021_at 0.735 ZNF532 Zinc finger protein 532 209040_s_at 0.735 PSMB8 Proteasome (prosome, macropain) subunit, beta type, 8 209676_at 0.735 TFPI Tissue factor pathway inhibitor 201675_at 0.736 AKAP1 A kinase (PRKA) anchor protein 1 204836_at 0.736 GLDC Glycine dehydrogenase 209539_at 0.736 ARHGEF6 Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6 202672_s_at 0.736 ATF3 isoform 3 is encoded by transcript variant 3 209906_at 0.736 C3AR1 Complement component 3a receptor 1 219232_s_at 0.736 EGLN3 Egl nine homolog 3 (C. elegans) 227697_at 0.736 SOCS3 Suppressor of cytokine signaling 3 212063_at 0.737 CD44 CD44 antigen (homing function and Indian blood group syste 225931_s_at 0.737 C17orf27 open reading frame 27 228338_at 0.737 LOC120376 Hypothetical protein LOC120376 1553043_a_a 0.737 CD300LF CD300 antigen like family member F 218901_at 0.737 PLSCR4 4 212014_x_at 0.738 CD44 CD44 antigen (homing function and Indian blood group syste 206696_at 0.738 GPR143 G protein-coupled receptor 143 206207_at 0.738 CLC Charcot-Leyden crystal protein 242037_at 0.738 ASPH Aspartate beta-hydroxylase 225929_s_at 0.739 C17orf27 Chromosome 17 open reading frame 27 224916_at 0.74 LOC340061 Hypothetical protein LOC340061 209500_x_at 0.74 TNFSF13 Tumor necrosis factor (ligand) superfamily, member 12 1553589_a_a 0.741 PDZK1IP1 PDZK1 interacting protein 1 1552789_at 0.741 TLOC1 Translocation protein 1 218396_at 0.741 VPS13C Vacuolar protein sorting 13C (yeast) 225105_at 0.742 LOC387882 LOC387882 hypothetical protein 218543_s_at 0.742 PARP12 Poly (ADP-ribose) polymerase family, member 12 227467_at 0.742 RDH10 Retinol dehydrogenase 10 (all-trans) 228094_at 0.742 AMICA1 Adhesion molecule, interacts with CXADR antigen 1 223220_s_at 0.742 PARP9 Poly (ADP-ribose) polymerase family, member 9 205250_s_at 0.743 Cep290 Centrosome protein cep290 203881_s_at 0.743 DMD (muscular dystrophy, Duchenne and Becker types 232336_at 0.743 ZSWIM5 Zinc finger, SWIM-type containing 5 209940_at 0.743 PARP3 Poly (ADP-ribose) polymerase family, member 3 202357_s_at 0.744 BF B-factor, properdin 203213_at 0.744 CDC2 Cell division cycle 2, G1 to S and G2 to M 210416_s_at 0.745 CHEK2 CHK2 checkpoint homolog (S. pombe) 202351_at 0.745 ITGAV Integrin, alpha V 205997_at 0.745 ADAM28 A disintegrin and metalloproteinase domain 28 215343_at 0.745 KIAA1509 KIAA1509 210095_s_at 0.745 IGFBP3 Insulin-like growth factor binding protein 3 229390_at 0.745 LOC441168 Hypothetical protein LOC441168 202963_at 0.745 RFX5 Regulatory , 5 (influences HLA class II expression) 204526_s_at 0.745 TBC1D8 TBC1 domain family, member 8 (with GRAM domain) 202748_at 0.746 GBP2 Guanylate binding protein 2, interferon-inducible 205968_at 0.746 KCNS3 Potassium voltage-gated channel, delayed-rectifier, subfamily 209684_at 0.746 RIN2 Ras and Rab interactor 2 230526_at 0.746 TNRC6C Trinucleotide repeat containing 6C 230104_s_at 0.746 TPPP -specific protein p25 alpha 201859_at 0.747 PRG1 Proteoglycan 1, secretory granule 236045_x_at 0.747 LOC441801 205159_at 0.748 CSF2RB Colony stimulating factor 2 receptor, beta, low-affinity 231234_at 0.748 CTSC Cathepsin C 204547_at 0.749 RAB40B RAB40B, member RAS oncogene family 203887_s_at 0.749 THBD Thrombomodulin 223710_at 0.749 CCL26 Chemokine (C-C motif) ligand 26 225647_s_at 0.75 CTSC Cathepsin C 221766_s_at 0.75 FAM46A Family with sequence similarity 46, member A 226604_at 0.75 SMILE SMILE protein 209301_at 0.75 CA2 Carbonic anhydrase II 209835_x_at 0.751 CD44 CD44 antigen (homing function and Indian blood group syste 206682_at 0.751 CLEC10A C-type lectin domain family 10, member A 222610_s_at 0.751 S100PBPR S100P binding protein Riken 209716_at 0.752 CSF1 Colony stimulating factor 1 (macrophage) 219630_at 0.752 PDZK1IP1 PDZK1 interacting protein 1 242790_at 0.752 EAP30 EAP30 subunit of ELL complex 221879_at 0.753 CALML4 200704_at 0.753 LITAF Lipopolysaccharide-induced TNF factor 226287_at 0.753 CCDC34 NY-REN-41 antigen 235438_at 0.753 MGC14595 Hypothetical protein MGC14595 226534_at 0.754 KITLG KIT ligand 204174_at 0.754 ALOX5AP Arachidonate 5-lipoxygenase-activating protein 232297_at 0.754 KLHL5 Kelch-like 5 (Drosophila) 225646_at 0.755 CTSC isoform b precursor is encoded by transcript variant 2 242662_at 0.755 PCSK6 Proprotein convertase subtilisin/kexin type 6 222847_s_at 0.756 EGLN3 Egl nine homolog 3 (C. elegans) 226148_at 0.756 HSPC063 BTB (POZ) domain containing 15 214830_at 0.756 SLC38A6 Solute carrier family 38, member 6 208966_x_at 0.756 IFI16 Interferon, gamma-inducible protein 16 204438_at 0.756 MRC1 Mannose receptor, C type 1 223620_at 0.757 GPR34 217764_s_at 0.757 RAB31 RAB31, member RAS oncogene family 203888_at 0.757 THBD Thrombomodulin 210102_at 0.757 LOH11CR2A Loss of heterozygosity, 11, chromosomal region 2, gene A 215425_at 0.758 BTG3 BTG family, member 3 219938_s_at 0.758 PSTPIP2 Proline-serine-threonine phosphatase interacting protein 2 202605_at 0.759 GUSB Glucuronidase, beta 226785_at 0.759 ATP11C ATPase, Class VI, type 11C 213682_at 0.759 NUP50 50kDa 208942_s_at 0.759 TLOC1 Translocation protein 1 221865_at 0.76 C9orf91 Chromosome 9 open reading frame 91 204646_at 0.761 DPYD Dihydropyrimidine dehydrogenase 239606_at 0.762 GCNT2 Glucosaminyl (N-acetyl) transferase 2, I-branching enzyme 209103_s_at 0.762 UFD1L 203596_s_at 0.763 IFIT5 Interferon-induced protein with tetratricopeptide repeats 5 203066_at 0.763 GALNAC4S-6ST B cell RAG associated protein 225330_at 0.763 217371_s_at 0.764 IL15 Interleukin 15 226702_at 0.764 205590_at 0.764 RASGRP1 RAS guanyl releasing protein 1 (calcium and DAG-regulated) 236979_at 0.765 C1orf178 Chromosome 1 open reading frame 178 206932_at 0.767 CH25H Cholesterol 25-hydroxylase 204389_at 0.768 MAOA Monoamine oxidase A 204490_s_at 0.769 CD44 CD44 antigen (homing function and Indian blood group syste 201422_at 0.769 IFI30 Interferon, gamma-inducible protein 30 220330_s_at 0.769 SAMSN1 SAM domain, SH3 domain and nuclear localisation signals, 1 227565_at 0.769 WHSC1 Wolf-Hirschhorn syndrome candidate 1 228771_at 0.77 ADRBK2 Adrenergic, beta, receptor kinase 2 201506_at 0.771 TGFBI Transforming growth factor, beta-induced, 68kDa 202953_at 0.771 C1QB Complement component 1, q subcomponent, beta polypeptid 222793_at 0.772 DDX58 DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 231928_at 0.772 HES2 Hairy and enhancer of split 2 (Drosophila) 221087_s_at 0.773 APOL3 Apolipoprotein L, 3 204900_x_at 0.775 SAP30 Sin3-associated polypeptide, 30kDa 210916_s_at 0.776 CD44 CD44 antigen (homing function and Indian blood group syste 1552477_a_a 0.776 IRF6 Interferon regulatory factor 6 222494_at 0.777 CHES1 Checkpoint suppressor 1 235256_s_at 0.777 GALM Galactose mutarotase (aldose 1-epimerase) 213772_s_at 0.777 GGA2 Golgi associated, gamma adaptin ear containing 202698_x_at 0.778 COX4I1 Cytochrome c oxidase subunit IV isoform 1 225951_s_at 0.779 CHD2 Chromodomain helicase DNA binding protein 2 204388_s_at 0.779 MAOA Monoamine oxidase A 204859_s_at 0.78 APAF1 Apoptotic protease activating factor 226001_at 0.78 KLHL5 Kelch-like 5 (Drosophila) 229572_at 0.78 Transcribed locus, moderately similar to XP_508230.1 PREDIC 228372_at 0.783 C10orf128 Chromosome 10 open reading frame 128 225188_at 0.784 RAPH1 Ras association (RalGDS/AF-6) and pleckstrin homology dom 236347_at 0.785 MMAA Methylmalonic aciduria (cobalamin deficiency) cblA type 204821_at 0.785 BTN3A3 Butyrophilin, subfamily 3, member A3 219209_at 0.786 IFIH1 Interferon induced with helicase C domain 1 229912_at 0.788 SDK1 Sidekick homolog 1 (chicken) 228046_at 0.788 LOC152485 Hypothetical protein LOC152485 226308_at 0.791 NY-SAR-48 Sarcoma antigen NY-SAR-48 203860_at 0.792 PCCA Propionyl Coenzyme A carboxylase, alpha polypeptide 204591_at 0.792 CHL1 Cell adhesion molecule with homology to L1CAM 226525_at 0.792 NTRK3 Neurotrophic tyrosine kinase, receptor, type 3 242013_at 0.792 208913_at 0.795 GGA2 Golgi associated, gamma adaptin ear containing 205890_s_at 0.796 UBD Ubiquitin D 226175_at 0.798 TTC9C Hypothetical protein MGC29649 227525_at 0.799 GLCCI1; GIG18 GIG18; Homo sapiens glucocorticoid induced transcript 1 203981_s_at 0.8 ABCD4 ATP-binding cassette, sub-family D (ALD), member 4 227702_at 0.8 CYP4X1 Cytochrome P450, family 4, subfamily X, polypeptide 1 232231_at 0.803 RUNX2 Runt-related transcription factor 2 209541_at 0.809 IGF1 Insulin-like growth factor 1 (somatomedin C) 230405_at 0.81 LOC441109 Hypothetical gene supported by AL713721 213194_at 0.82 ROBO1 Roundabout, guidance receptor, homolog 1 (Drosophila) 218804_at 0.82 TMEM16A Transmembrane protein 16A 205992_s_at 0.821 IL15 Interleukin 15 202491_s_at 0.828 IKBKAP Inhibitor of kappa light polypeptide gene enhancer in B-cells # Affy lung Eso Symbol Gene name 1300019J08Rik 453 1450826_a_at 104.7 9.034 Saa3 Serum amyloid2310047C04Rik A 3 413 1449153_at 83.05 41.8 Mmp12 Matrix metalloproteinase9530010C24Rik 12 210 1425295_at 52.08 28.71 Ear11 Eosinophil-associated,A930031D07Rik ribonuclease A family, member 11 284 1418932_at 31.18 4.653 Nfil3 Nuclear factor, Il1r2interleukin 3, regulated 267 1442798_x_at 24.02 2.376 Hk3 Hexokinase 3 1110008F13Rik 182 1425450_at 23.36 46.61 Chi3l4 Chitinase 3-likeBC004044 4 352 1424509_at 21.97 8.758 Cd177 Hypothetical proteinPrkcd MGC48079 222 1459970_at 21.15 2.146 Ust RIKEN cDNA 4930573G07Gria2 gene 174 1418165_at 20.51 25.43 Itlna Intelectin a 5830411E10Rik 449 1417789_at 19.21 3.827 Ccl11 Small chemokine (C-C motif38413) ligand 11 245 1448898_at 17.72 1.937 Ccl9 Chemokine (C-CTmem35 motif) ligand 9 162 1449143_at 17.37 4.19 5830458K16RikRIKEN cDNA 5830458K16Dpysl4 gene 252 1417936_at 17.2 2.479 Ccl9 Chemokine (C-CA930006A01Rik motif) ligand 9 225 1421307_at 16.94 1.188 Car13 Carbonic anhydrPrtn3ase 13 227 1443126_at 16.53 1.508 Slc12a1 Solute carrier family 12, member 1 291 1436530_at 16.25 2.707 CDNA clone MGC:107680Surf4 IMAGE:6766535 402 1419684_at 16.04 11.11 Ccl8 Chemokine (C-CLOC225443 motif) ligand 8 364 1448767_s_at 15.86 4.613 Gjb1 Gap junction membrGja5 ane channel protein beta 1 232 1435761_at 14.92 2.57 Stfa1 Stefin A1 Atp6v0d2 268 1418645_at 14.49 2.068 Hal Histidine ammoniaRarres1 lyase 459 1447380_at 14.28 1.451 1300019J08RikRIKEN cDNA 1300019J081110028A07Rik gene 178 1427747_a_at 13.9 14.23 Lcn2 Lipocalin 2 Retnla 265 1422648_at 13.75 1.919 Slc7a2 Solute carrier familyF730015K02Rik 7 (cationic amino acid transporter, y+ system), member 2 194 1436439_at 13.7 13.36 1700016G14RikAV266901 RIKENGalnt7 full-length enriched, adult male testis (DH10B) Mus musculus cDNA clone 4930521G13 3', mRNA sequence. 299 1435409_at 13.23 2.296 Transcribed locusCyba 287 1427221_at 12.84 3.11 Xtrp3s1 X transporter proteinGda 3 similar 1 gene 416 1451537_at 12.49 8.783 Chi3l1 Chitinase 3-likeSlc6a2 1 351 1458299_s_at 12.44 4.889 Nfkbie Nuclear factor ofLm kappayc1 light polypeptide gene enhancer in B-cells inhibitor, epsilon 293 1451715_at 11.82 2.497 Mafb V- musculoaponeuroticOlfm3 fibrosarcoma oncogene family, protein B (avian) 233 1460282_at 11.59 2.628 Trem1 Triggering receptor expressed on myeloid cells 1 270 1455332_x_at 11.1 2.235 Fcgr2b Fc receptor, IgG,Epha5 low affinity IIb 271 1451941_a_at 10.85 2.403 Fcgr2b Fc receptor, IgG,2810416A17Rik low affinity IIb 281 1437611_x_at 10.76 2.071 Kif2c Kinesin family memberCcl11 2C 427 1420394_s_at 10.6 3.869 Gp49a Glycoprotein 49Bub1b A 296 1418930_at 10.46 2.084 Cxcl10 Chemokine (C-XMy-Co9b motif) ligand 10 439 1435477_s_at 10.1 3.493 Fcgr2b Fc receptor, IgG,Mmp12 low affinity IIb 426 1421802_at 9.999 3.724 Ear1 Eosinophil-associated,Psmb8 ribonuclease A family, member 2 229 1439016_x_at 9.984 1.615 Sprr2a Small proline-richCcl25 protein 2A 433 1420249_s_at 9.882 3.64 Ccl6 Chemokine (C-CScn1b motif) ligand 6 256 1460227_at 9.335 2.559 Timp1 Tissue inhibitorR ofalgps1 metalloproteinase 1 163 1419669_at 9.23 8.486 Prtn3 Ptk6 176 1449156_at 9.077 9.672 Ly9 Lymphocyte antigen1200003I10Rik 9 444 1421326_at 8.942 3.765 Csf2rb1 Colony stimulatingNpas2 factor 2 receptor, beta 1, low-affinity (granulocyte-macrophage) 290 1449015_at 8.875 2.195 Retnla Resistin like alphaRusc2 357 1445943_at 8.84 4.814 H3103A01-3 NIAAntxr2 Mouse 15K cDNA Clone Set Mus musculus cDNA clone H3103A01 3', mRNA sequence. 386 1436251_at 8.738 8.737 Pde1c isoform b is encodedEar1 by transcript variant 2; go_function: calmodulin binding [goid 0005516] [evidence IEA]; go_function: hydrolase activity [goid 0016787] [evidence IEA]; go_function: 3',5'-cyclic-nucleotide activity [goid 0004114] [evidence IEA]; go_process: signal transduction [goid 0007165] [evidence IEA]; Mus musculus phosphodiesterase 1C (Pde1c), transcript variant 2, mRNA. 321 1445458_at 8.703 52.67 mRNA for evolutionary breakpoint region transcript 1 282 1429947_a_at 8.407 2.025 Zbp1 Z-DNA binding Chi3l3protein 1 191 1446558_at 8.352 33.62 F730015K02RikRIKEN cDNA F730015K02Es1 gene 418 1434798_at 8.335 4.968 Atp6v0d2 RIKEN cDNA 4833419A21Sprr2j gene 431 1427682_a_at 8.128 3.364 Egr2 Early growth responseXtrp3s1 2 269 1427313_at 8.116 1.849 Ptgir Prostaglandin I Ebi3receptor (IP) 295 1417601_at 8.077 2.213 Rgs1 Regulator of G-proteinRgs20 signaling 1 203 1424923_at 7.901 4.852 Serpina3g Serine (or cysteine)Stfa1 proteinase inhibitor, clade A, member 3G 303 1419430_at 7.853 1.799 Cyp26a1 Cytochrome P450,1700023L04Rik family 26, subfamily a, polypeptide 1 184 1431808_a_at 7.681 42.06 Itih4 Inter alpha-trypsinCalm3 inhibitor, heavy chain 4 240 1422790_at 7.485 2.214 Nppc Natriuretic peptideBirc3 precursor type C 406 1427575_at 7.359 4.089 Fbxw14 F-box and WD-40Msmb domain protein 14 185 1444176_at 7.237 17.68 Atp6v0d2 RIKEN cDNA 4833419A21Cckar gene 278 1424754_at 7.009 2.009 Ms4a7 synonyms: CFFMA,Sprr2a CD20l4, 9130422I10Rik, A430103C15Rik; isoform b is encoded by transcript variant 2; Mus musculus membrane-spanning 4-domains, subfamily A, member 7 (Ms4a7), transcript variant 2, mRNA. 285 1421687_at 7.004 2.649 Msmb Beta-microseminoproteinSelpl 422 1419128_at 6.871 4.07 Itgax Integrin alpha XC77097 171 1445967_at 6.733 6.306 AU022331 Integrin alpha 9Ptpn21 399 1430824_at 6.691 5.059 Arhgap23 Rho GTPase activating protein 23 391 1419004_s_at 6.678 6.148 Bcl2a1a B-cell leukemia/lymphomaRrs1 2 related protein A1a 389 1436712_at 6.665 6.142 Pla2g4c ,Pttg1 group IVC (cytosolic, calcium-independent) 274 1442082_at 6.659 2.018 C3ar1 Complement componentFdps 3a receptor 1 193 1449305_at 6.618 5.547 F10 Coagulation factorZfhx4 X 192 1418992_at 6.606 12.92 F10 Coagulation factor X 348 1458051_at 6.582 8.205 A230048O21RikRIKEN cDNA 0910001A06Dab1 gene 452 1449360_at 6.569 2.732 Csf2rb2 Colony stimulatingSyt6 factor 2 receptor, beta 2, low-affinity (granulocyte-macrophage) 226 1443071_at 6.385 1.254 AI839979 Adult male bonePapss2 cDNA, RIKEN full-length enriched library, clone:9830168M11 :unknown EST, full insert sequence 425 1449164_at 6.349 2.912 Cd68 CD68 antigen Kbtbd9 243 1443827_x_at 6.349 1.557 BC004044 CDNA sequenceOdz4 BC004044 272 1418248_at 6.332 1.689 Gla Galactosidase, C77144alpha 392 1420699_at 6.269 5.388 Clec7a C-type lectin domainEln family 7, member a 223 1459145_at 6.23 1.205 A930033H14RikRIKEN cDNA A930033H14Sorbs1 gene 289 1419254_at 6.214 2.258 Mthfd2 MethylenetetrahMkl2ydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase 201 1450485_at 6.056 3.6 Sox3 SRY-box containingZbtb16 gene 3 231 1433018_at 5.838 1.89 4930560O18RikRIKEN cDNA 8430420C20H2-Q1 gene # Affy lung Eso Symbol Gene name 1300019J08Rik 412 1455660_at 5.803 4.201 Csf2rb1 Colony stimulatingAgtr2 factor 2 receptor, beta 1, low-affinity (granulocyte-macrophage) 312 1418993_s_at 5.717 46.27 F10 Coagulation factorGadd45g X 454 1417314_at 5.633 2.146 H2-Bf HistocompatibilitCasp14y 2, complement component factor B 353 1458765_at 5.61 2.972 Rbm10 RNA binding motif protein 10 129 1419783_at 5.576 3.443 AV259294 RIKENEhf full-length enriched, adult male testis (DH10B) Mus musculus cDNA clone 4930404E11 3', mRNA sequence. 276 1419483_at 5.544 1.944 C3ar1 Complement componentLrp12 3a receptor 1 273 1419599_s_at 5.438 1.957 Ms4a11 Membrane-spanningPlek2 4-domains, subfamily A, member 6D 259 1437716_x_at 5.396 2.092 Kif22 Kinesin family memberPlek 22 368 1434067_at 5.228 3.683 AI662270 uw45e08.x1 Soares_mammary_gland_NMLMGTgtp Mus musculus cDNA clone IMAGE:3464966 3', mRNA sequence. 190 1424265_at 5.176 7.978 Npl N-acetylneuraminateTrim27 pyruvate lyase 262 1448756_at 4.956 47.52 S100a9 S100 calcium bindingGal protein A9 (calgranulin B) 246 1435476_a_at 4.931 39.43 Fcgr2b Fc receptor, IgG,Csf2rb1 low affinity IIb 415 1448575_at 4.781 35.23 Il7r Interleukin 7 receptorStk25 441 1429954_at 4.759 32.07 Clec4a3 C-type lectin domainEar3 family 4, member a3 440 1451716_at 4.753 31.63 Mafb V-maf musculoaponeuroticC76434 fibrosarcoma oncogene family, protein B (avian) 292 1417870_x_at 4.743 30.14 Ctsz Cathepsin Z Padi1 339 1422061_at 4.681 22.69 Akr1c20 Aldo-keto reductaseRnf180 family 1, member C20 380 1422784_at 4.651 16.3 Krt2-6a Keratin complexPfc 2, basic, gene 6a 382 1444707_at 4.638 12.93 Transcribed locus1700010A17Rik 434 1419620_at 4.633 12.26 Pttg1 Pituitary tumor-trGrin2bansforming 1 446 1421074_at 4.611 10.69 Cyp7b1 Cytochrome P450,Plek family 7, subfamily b, polypeptide 1 150 1420558_at 4.571 10.18 Selp Selectin, platelet4931407J08Rik 275 1456212_x_at 4.558 9.935 Socs3 Suppressor of cytokineSnrpn signaling 3 355 1460038_at 4.553 9.753 Pou3f1 POU domain, classPtgfr 3, transcription factor 1 432 1417266_at 4.518 9.679 Ccl6 Chemokine (C-CC530044N13Rik motif) ligand 6 154 1419482_at 4.433 9.557 C3ar1 Complement component4833417J20Rik 3a receptor 1 202 1448789_at 4.325 9.362 Aldh1a3 Aldehyde dehydrogenaseYars family 1, subfamily A3 304 1449363_at 4.311 9.193 Atf3 Activating transcriptionFcmd factor 3 419 1428572_at 4.218 8.577 Basp1 Brain abundant,G431001E03Rik membrane attached signal protein 1 345 1449508_at 4.198 8.376 Il27ra Interleukin 27 receptorAsb15 , alpha 261 1417244_a_at 4.164 8.223 Irf7 Interferon regulatoryHmox1 factor 7 126 1421061_at 4.144 8.203 Guca1a Guanylate cyclaseSelp activator 1a (retina) 241 1447490_at 4.111 7.853 Transcribed locusPopdc2 450 1448748_at 4.088 7.558 Plek Pleckstrin Gsta1 313 1422963_at 4.076 7.359 Sprr2i Small proline-richSgol1 protein 2I 213 1441326_at 4.075 7.332 Cp Ceruloplasmin Nup98 311 1425451_s_at 4.043 7.25 Chi3l3 Chitinase 3-likeCcna2 3 170 1450200_s_at 4.038 7.223 Csf2rb1 Colony stimulatingEpas1 factor 2 receptor, beta 1, low-affinity (granulocyte-macrophage) 288 1455899_x_at 3.985 7.157 Socs3 Suppressor of cytokineGm67 signaling 3 456 1460437_at 3.965 6.931 Pscd4 Pleckstrin homologyVldlr , Sec7 and coiled/coil domains 4 360 1431591_s_at 3.881 6.874 G1p2 Interferon, alpha-inducibleTnfrsf1b protein 405 1448561_at 3.847 6.865 Ncf2 Neutrophil cytosolicChit1 factor 2 234 1438434_at 3.846 6.516 Arhgap11a Rho GTPase activIsl1ating protein 11A 370 1434955_at 3.834 5.907 1-Mar Membrane-associatedCcl8 ring finger (C3HC4) 1 297 1435644_at 3.804 5.519 G431001E03RikRIKEN cDNA G431001E03Il7r gene 363 1434773_a_at 3.797 5.398 Slc2a1 Solute carrier familyPlek 2 (facilitated glucose transporter), member 1 # Affy lung Eso Symbol Gene name 1300019J08Rik 788 1421100_a_at 0.0185 0.109 Dab1 Disabled homologSh3bp2 1 (Drosophila) 609 1429759_at 0.028 0.153 Rps6ka6 synonyms: RSK4,F2rl2 2610524K04Rik; go_function: ATP binding [goid 0005524] [evidence ISS] [pmid 12466851]; go_function: kinase activity [goid 0016301] [evidence IEA]; go_function: protein kinase activity [goid 0004672] [evidence ISS] [pmid 12466851]; go_function: structural constituent of ribosome [goid 0003735] [evidence IEA]; go_function: protein-tyrosine kinase activity [goid 0004713] [evidence ISS] [pmid 12466851]; go_function: protein serine/threonine kinase activity [goid 0004674] [evidence ISS] [pmid 12466851]; go_process: protein amino acid phosphorylation [goid 0006468] [evidence ISS] [pmid 12466851]; Mus musculus ribosomal protein S6 kinase polypeptide 6 (Rps6ka6), mRNA. 797 1459995_at 0.0308 0.0988 1700015G11RikRIKEN cDNA 1700015G11Olfml1 gene 779 1448973_at 0.0365 0.0584 Sult1d1 SulfotransferaseTef family 1D, member 1 586 1460256_at 0.0388 0.731 Car3 Carbonic anhydrTimp3ase 3 778 1438358_x_at 0.0442 0.067 Pfdn5 Prefoldin 5 Rgs7 821 1445962_at 0.0442 0.149 Gria2 Glutamate receptorSectm1, ionotropic, AMPA2 (alpha 2) 656 1441897_at 0.0469 0.479 B230120H23RikRIKEN cDNA B230120H23Cyp2c39 gene 585 1437232_at 0.047 0.816 Bpil2 Bactericidal/permeabilitClec4a3 y-increasing protein-like 2 760 1436148_at 0.0476 0.0788 Transcribed locusCtss 661 1429358_at 0.0503 0.536 4921533L14RikRIKEN cDNA 4921533L14Spp1 gene 653 1443070_at 0.0546 0.667 Auts2 Autism susceptibilitItga8y candidate 2 654 1420431_at 0.056 0.75 Rptn Repetin LOC433723 665 1424178_at 0.058 0.549 Tmem38a TransmembraneAp1s2 protein 38a 677 1444504_at 0.059 0.663 1110001P11RikRP23-338M9.5;Pnmt go_function: activity [goid 0016491] [evidence IEA]; Mus musculus RIKEN cDNA 1110001P11 gene (1110001P11Rik), mRNA. 588 1421559_at 0.0597 0.475 Abo ABO blood groupAU022331 (transferase A, alpha 1-3-N-acetylgalactosaminyltransferase, transferase B, alpha 1-3-galactosyltransferase) 649 1449823_at 0.0627 0.441 Dach2 Dachshund 2 (Drosophila)BC054438 619 1446864_at 0.0639 0.14 Yars Tyrosyl-tRNA synthetaseD830036C21Rik 801 1421289_at 0.065 0.446 Hspb7 Heat shock protein2310022A10Rik family, member 7 (cardiovascular) 659 1441874_x_at 0.0663 0.615 Prlpe Prolactin-like proteinBC034068 E 787 1456127_at 0.0739 0.238 9630008K15RikRIKEN cDNA 9630008K15Ttpa gene 672 1444444_at 0.0748 0.681 16 days neonateCdc2l6 heart cDNA, RIKEN full-length enriched library, clone:D830025C17 product:unclassifiable, full insert sequence 666 1419215_at 0.0819 0.512 Aox4 Aldehyde oxidaseFox 4d3 671 1418199_at 0.0831 0.639 Hemgn Hemogen Tnfaip8 695 1459647_at 0.0873 0.169 Pold3 Polymerase (DNAAcsl1-directed), delta 3, accessory subunit 655 1425677_a_at 0.0897 0.813 Ank1 Ankyrin 1, erythroidCdca3 624 1437386_at 0.0927 0.366 Lrrn6a Leucine rich repeatP2ry6 neuronal 6A 621 1418174_at 0.0932 0.338 Dbp D site albumin Mab21l1promoter binding protein 664 1440523_at 0.0955 0.621 Rdhe2 Retinal short chainBcas2 dehydrogenase reductase 2 707 1442236_at 0.101 0.0499 Za20d3 Zinc finger, A202310047N11Rik domain containing 3 830 1420201_at 0.103 0.293 BB088844 RIKENNme7 full-length enriched, 12 days embryo, embryonic body between diaphragm region and neck Mus musculus cDNA clone 9430019A13 3' similar to AF170284 Rattus norvegicus connexin 30 mRNA, mRNA sequence. 673 1425792_a_at 0.113 0.62 Rorc RAR-related orphanCcl9 receptor gamma 622 1416710_at 0.114 0.348 Tmem35 TransmembraneMybph protein 35 831 1449828_at 0.115 0.305 Ptgfr Prostaglandin FRdhe2 receptor 635 1420512_at 0.121 0.348 Dkk2 Dickkopf homologRspo3 2 (Xenopus laevis) 824 1420349_at 0.124 0.33 Ptgfr Prostaglandin FGuca1a receptor 829 1447462_at 0.125 0.256 D7Wsu130e DNA segment, AI449441Chr 7, Wayne State University 130, expressed 637 1457203_at 0.125 0.276 Transcribed locusPfdn5 747 1430588_at 0.128 0.17 Mro Maestro 763 1443531_at 0.129 0.191 A930005I04RikRIKEN cDNA A930005I042310021H06Rik gene 802 1457076_at 0.131 0.486 LOC277743 Gene model 693,9030611N15Rik (NCBI) 620 1438211_s_at 0.135 0.354 Dbp D site albumin 2610307O08Rikpromoter binding protein 768 1429956_at 0.137 0.256 1700021K02RikRIKEN cDNA 1700021K02Ear2 gene 701 1438124_at 0.138 0.072 LOC381064 Similar to putativBC032204e pheromone receptor 727 1420271_at 0.143 0.0615 Transcribed locusMefv 818 1426134_at 0.144 0.375 Trdn Triadin Irf7 791 1449486_at 0.145 0.308 Ces1 CarboxylesteraseDach2 1 705 1456095_at 0.15 0.152 Tyr Transcribed locus 607 1432923_at 0.151 0.344 2810404I24RikRIKEN cDNA 2810404I24H2-Aa gene 716 1432950_at 0.152 0.187 5330421F21RikSolute carrier familyAI662270 24 (sodium/potassium/calcium exchanger), member 2 746 1439593_s_at 0.154 0.15 C030010B13RikRIKEN cDNA C030010B13Gucy1a2 gene 799 1430550_at 0.162 0.507 Lipl3 -like, ab-hAI848258ydrolase domain containing 3 751 1444187_at 0.164 0.157 LOC544917 Derived by automatedAI854517 computational analysis using gene prediction method: GNOMON. Supporting evidence includes similarity to: 1 mRNA; PREDICTED: Mus musculus similar to spermatogenesis associated glutamate (E)-rich protein 4b (LOC544917), mRNA. 651 1460281_at 0.169 0.438 Asb15 Ankyrin repeatD7Wsu130e and SOCS box-containing protein 15 726 1456455_at 0.171 0.0993 Lpp Mortality factor1700021K02Rik 4 like 1 577 1416913_at 0.173 0.327 Es1 1 3300001K11Rik 723 1449962_at 0.174 0.0509 Pramel3 Preferentially expressedXpo4 antigen in melanoma-like 3 736 1418138_at 0.175 0.053 Sult1d1 SulfotransferaseMyl2 family 1D, member 1 694 1441699_at 0.179 0.257 Atp8b2 Atpase, class I,Defb3 type 8B, member 2 693 1422904_at 0.187 0.237 Fmo2 Flavin containingSerpina3g monooxygenase 2 618 1422192_at 0.191 0.282 Gja5 Gap junction membrChi3l4ane channel protein alpha 5 713 1440251_s_at 0.193 0.216 Zfp64 Zinc finger proteinCrispld2 64 731 1441854_at 0.195 0.0611 Pole Polymerase (DNATectb directed), epsilon 807 1446680_at 0.198 0.539 H3117E10-3 NIADsc1 Mouse 15K cDNA Clone Set Mus musculus cDNA clone H3117E10 3', mRNA sequence. # Affy lung Eso Symbol Gene name 1300019J08Rik 466 1419875_at 0.01 1.98 Transcribed locusFut2 483 1439865_at 0.0348 4.879 na synonym: 1110008P08Rik;Npb kelch repeat and BTB (POZ) domain containing 7-like; Mus musculus gene model 295, (NCBI) (Gm295), mRNA. 513 1457631_at 0.0354 12.75 2310047N11RikMus musculus Timp3adult male tongue cDNA, RIKEN full-length enriched library, clone:2310047N11 product:unknown EST, full insert sequence. 486 1459437_at 0.0497 1.695 Stard9 RIKEN cDNA 4831403C07Cdh13 gene 489 1458219_at 0.0524 3.007 Bcas2 Breast carcinomaAcsl1 amplified sequence 2 559 1419530_at 0.0598 15.11 Il12b Interleukin 12bSpink5 464 1459204_at 0.0731 1.478 AU015449 H3085E12-3 NIA Mouse 15K cDNA Clone Set 517 1436432_at 0.0809 5.458 B230343J05RikRIKEN cDNA B230343J05Gp49a gene 556 1459359_at 0.095 13.56 0 day neonate Hspb7cerebellum cDNA, RIKEN full-length enriched library, clone:C230091N23 product:unclassifiable, full insert sequence 525 1432316_at 0.0987 3.438 4933439N14RikRIKEN cDNA 4933439N14C1r gene 557 1434527_at 0.107 19.74 Nalp4b DNA segment, Clec7aChr 7, ERATO Doi 595, expressed 488 1430118_at 0.109 1.435 2700046A07RikRIKEN cDNA 2700046A07Mrgpra4 gene 528 1429342_s_at 0.112 4.258 2310021H06RikRIKEN cDNA 2310021H06Coro1a gene 509 1421363_at 0.113 13.78 Cyp2c39 Cytochrome P450,Adamts4 family 2, subfamily c, polypeptide 39 474 1445986_at 0.123 3.286 C86195 H3053H08-3 NIAG630055G22Rik Mouse 15K cDNA Clone Set Mus musculus cDNA clone H3053H08 3', mRNA sequence. 516 1458283_at 0.133 3.06 4931406P16RikRIKEN cDNA 4931406P16Ces1 gene 473 1457236_at 0.153 4.453 4933402E03RikPoly(rC) bindingIl1f5 protein 4 465 1435760_at 0.155 1.197 MGI:3524930 Cystatin A Lcp2 472 1449780_at 0.159 3.676 BB182666 RIKENFgfr4 full-length enriched, adult male hypothalamus Mus musculus cDNA clone A230099J04 3' similar to AB016536 Rattus norvegicus mRNA for AlF-C1, mRNA sequence. 492 1447803_x_at 0.161 1.793 Capg Capping protein4930423O20Rik (actin filament), gelsolin-like 496 1431905_s_at 0.165 1.661 4933427G17RikRIKEN cDNA 4933427G172010004A03Rik gene 479 1459336_at 0.168 3.148 Gucy1a2 Guanylate cyclaseSlco5a1 1, soluble, alpha 2 527 1426621_a_at 0.184 2.512 Ppp2r2b synonyms: SCA12,Hal MGC113781, PR55-BETA, PP2A-PR55B, 2900026H06Rik, 6330404L05Rik; isoform 1 is encoded by transcript variant 1; Mus musculus (formerly 2A), regulatory subunit B (PR 52), beta isoform (Ppp2r2b), transcript variant 1, mRNA. 469 1453963_at 0.188 2.881 1600014C23RikRIKEN cDNA 1600014C23Pole gene 547 1432503_a_at 0.192 13.87 Pdcl2 Phosducin-like Gjb12 535 1456781_at 0.198 4.337 SRY-box containingCkmt2 gene 2 499 1446988_at 0.204 26.63 Nup98 Nucleoporin 98Car3 558 1427700_x_at 0.204 14.57 Krt2-6a Keratin complexSocs3 2, basic, gene 6a 468 1437169_at 0.205 13.32 Pdlim1 PDZ and LIM domainFcgr2b 1 (elfin) 463 1444129_at 0.215 12.63 Isl1 ISL1 transcriptionLphn3 factor, LIM/homeodomain (islet 1) 501 1429824_at 0.226 11.76 4930550C14RikRIKEN cDNA 4930550C14Ear5 gene 521 1428567_at 0.227 10 Hspbap1 Hspb associatedCx proteincl10 1 508 1435842_at 0.23 9.931 BC034068 CDNA sequenceBasp1 BC034068 514 1421765_at 0.231 9.247 Pax5 RIKEN cDNA 4930517J16Itlna gene 531 1454351_at 0.237 8.657 4933435C09RikMus musculus 3010022N24Rikadult male testis cDNA, RIKEN full-length enriched library, clone:4933435C09 product:unclassifiable, full insert sequence. 523 1427417_at 0.239 8.382 Scml4 Sex comb on midleg-likEdem1 e 4 (Drosophila) 563 1430832_at 0.241 7.804 4930426I24RikBB055339 RIKENFolr4 full-length enriched, 12 days embryo male wolffian duct Mus musculus cDNA clone 6720480K08 3', mRNA sequence. 540 1421301_at 0.242 7.275 Zic2 Zic finger protein5830458K16Rik of the cerebellum 2 551 1434531_at 0.244 6.537 GnT-IX Beta1,6-N-acetAI451557ylglucosaminyltransferase IX 462 1437435_at 0.246 6.345 1700061G19RikRIKEN cDNA 1700061G19P2rx4 gene 571 1435704_at 0.248 6.33 C920006O11RikRIKEN cDNA C920006O11Chi3l1 gene 467 1441712_at 0.254 6.275 C330046L10RikUbiquitin specific protease 49 541 1458988_at 0.255 6.068 Cdc2l6 Cell division cyLcleOC277743 2-like 6 (CDK8-like) 554 1441252_at 0.257 5.479 2010001A14RikRIKEN cDNA 2010001A14 gene 555 1436702_at 0.258 5.405 BC034068 CDNA sequenceCcl6 BC034068 568 1415809_at 0.26 5.395 Tpbpa Trophoblast specific protein alpha 507 1430912_a_at 0.268 5.383 Tectb Tectorin beta Akr1c20 512 1438150_at 0.275 5.306 Fdps Farnesyl diphosphateGalnt6 synthetase 524 1435296_at 0.278 5.207 Adra2c Adrenergic receptor5730592L21Rik, alpha 2c 562 1459399_at 0.278 5.117 Mus musculus Hpgd0 day neonate lung cDNA, RIKEN full-length enriched library, clone:E030038M17 product:unknown EST, full insert sequence. 552 1432346_a_at 0.282 5.08 Cdh23 Cadherin 23 (otocadherin)Aqp3 # Affy lung Eso Symbol Gene name 1300019J08Rik 81 1444979_at 20.76 0.219 H3103F07-3 NIAMuc10 Mouse 15K cDNA Clone Set Mus musculus cDNA clone H3103F07 3', mRNA sequence. 104 1430567_at 16.38 0.466 Spink5 Serine proteaseAnks1 inhibitor, Kazal type 5 33 1441268_at 14.47 0.0883 H2-Eb1 L0849C06-3 NIATbx3 Mouse Newborn Brain cDNA Library Mus musculus cDNA clone L0849C06 3', mRNA sequence. 36 1420239_x_at 12.69 0.122 38413 Membrane-associated1110037F02Rik ring finger (C3HC4) 2 71 1459554_at 12.56 0.217 H3067B11-3 NIAMfap3l Mouse 15K cDNA Clone Set Mus musculus cDNA clone H3067B11 3', mRNA sequence. 65 1444661_at 12.54 0.225 Gpr26 G protein-coupledPspc1 receptor 26 6 1435190_at 12.33 0.646 Chl1 Cell adhesion moleculeNek2 with homology to L1CAM 43 1437860_at 12.02 0.162 Prkce Protein kinase Arpc1bC, epsilon 49 1448394_at 11.42 0.0161 Myl2 Myosin, light polypeptide2810404I24Rik 2, regulatory, cardiac, slow 72 1426131_at 11.26 0.238 1700036D21RikRIKEN cDNA 1700036D21MGC27770 gene 75 1444341_at 10.08 0.463 8030451F13RikRIKEN cDNA 8030451F13Zic2 gene 78 1459110_at 9.536 0.345 Myo9b Myosin IXb Aoc3 98 1429643_a_at 9.112 0.452 Pde1c isoform b is encodedSlc25a31 by transcript variant 2; go_function: calmodulin binding [goid 0005516] [evidence IEA]; go_function: hydrolase activity [goid 0016787] [evidence IEA]; go_function: 3',5'-cyclic-nucleotide phosphodiesterase activity [goid 0004114] [evidence IEA]; go_process: signal transduction [goid 0007165] [evidence IEA]; Mus musculus phosphodiesterase 1C (Pde1c), transcript variant 2, mRNA. 16 1425251_at 8.944 0.24 Ptger3 Prostaglandin ENppc receptor 3 (subtype EP3) 21 1435621_at 8.929 0.154 Mlstd1 Male sterility domainHspa5 containing 1 73 1456152_at 8.918 0.498 Paqr5 Progestin and adipoQA930005I04Rik receptor family member V 117 1429067_at 8.771 0.501 Capns2 Calpain, small Cyp26a1subunit 2 31 1436162_at 8.108 0.0594 C730048C13RikRIKEN cDNA C730048C13Cd68 gene 109 1444043_at 7.979 0.764 Gli3 GLI-Kruppel familyPapss2 member GLI3 100 1431164_at 7.802 0.469 Rragd Ras-related GTPPde10a binding D 95 1453552_at 7.589 0.472 2310014F07RikRIKEN cDNA 2310014F07Pramel3 gene 5 1416632_at 6.955 0.702 Mod1 Malic enzyme, Exsupernatanto1 58 1453894_at 6.81 0.235 4933434C23RikRIKEN cDNA 4933434C23MGI:2388100 gene 9 1420779_at 6.744 0.754 Fhl3 Four and a halfCcnb2 LIM domains 3 107 1449424_at 6.615 0.753 Plek2 Pleckstrin 2 Hfe2 105 1449902_at 6.56 0.588 1110058A15RikRIKEN cDNA 1110058A15Suz12 gene 50 1449819_at 6.051 0.121 Dmc1h Disrupted meioticTgfbr3 cDNA 1 homolog 37 1449690_x_at 5.856 0.217 C77112 MouseT 3.5-dpcsc22d1 blastocyst cDNA Mus musculus cDNA clone J0026B10 3', mRNA sequence. 110 1450271_at 5.815 0.654 Ptk6 PTK6 protein tyrosine2410022L05Rik kinase 6 17 1445675_at 5.797 0.341 A830008O07 Hypothetical protein6820402A03Rik A830008O07 1 5.791 0.64 Serpinb2 Serine (or cysteine)Nalp10 proteinase inhibitor, clade B, member 2 97 1438280_at 5.424 0.419 1700023L04RikRIKEN cDNA 1700023L04Dsg1b gene 61 1438431_at 5.23 0.442 Abcd2 ATP-binding cassette,1700061G19Rik sub-family D (ALD), member 2 116 1434862_at 5.077 0.509 Fut2 FucosyltransferSlfn2ase 2 108 1422223_at 5.032 0.733 Grin2b Glutamate receptorAtp6v0d2, ionotropic, NMDA2B (epsilon 2) 48 1449320_at 4.812 0.0846 Pbsn Probasin 54 1423968_at 4.014 0.21 Ugt3a2 UDP glucuronosyltrLy86ansferase 3 family, polypeptide A2 26 1443714_at 3.364 0.154 C530044N13RikRIKEN cDNA C530044N134933435C09Rik gene 45 1457427_at 2.566 0.138 LOC230959 Gene model 573,Cdk5 (NCBI) 46 1430998_at 2.378 0.189 Sqrdl Sulfide quinoneC030002E08Rik reductase-like (yeast)