DOCSLIB.ORG

Mouse Inava Conditional Knockout Project (CRISPR/Cas9)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mouse Inava Conditional Knockout Project (CRISPR/Cas9) https://www.alphaknockout.com Mouse Inava Conditional Knockout Project (CRISPR/Cas9) Objective: To create a Inava conditional knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Inava gene (NCBI Reference Sequence: NM_028872.3 ; Ensembl: ENSMUSG00000041605 ) is located on Mouse chromosome 1. 10 exons are identified, with the ATG start codon in exon 1 and the TAA stop codon in exon 10 (Transcript: ENSMUST00000120339). Exon 2 will be selected as conditional knockout region (cKO region). Deletion of this region should result in the loss of function of the Mouse Inava gene. To engineer the targeting vector, homologous arms and cKO region will be generated by PCR using BAC clone RP23-100N3 as template. Cas9, gRNA and targeting vector will be co-injected into fertilized eggs for cKO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Exon 2 starts from about 10.04% of the coding region. The knockout of Exon 2 will result in frameshift of the gene. The size of intron 1 for 5'-loxP site insertion: 6240 bp, and the size of intron 2 for 3'-loxP site insertion: 609 bp. The size of effective cKO region: ~649 bp. The cKO region does not have any other known gene. Page 1 of 8 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele gRNA region 5' gRNA region 3' 1 2 3 4 5 10 Targeting vector Targeted allele Constitutive KO allele (After Cre recombination) Legends Exon of mouse Inava Homology arm cKO region loxP site Page 2 of 8 https://www.alphaknockout.com Overview of the Dot Plot Window size: 10 bp Forward Reverse Complement Sequence 12 Note: The sequence of homologous arms and cKO region is aligned with itself to determine if there are tandem repeats. No significant tandem repeat is found in the dot plot matrix. So this region is suitable for PCR screening or sequencing analysis. Overview of the GC Content Distribution Window size: 300 bp Sequence 12 Summary: Full Length(7149bp) | A(21.09% 1508) | C(26.47% 1892) | T(24.77% 1771) | G(27.67% 1978) Note: The sequence of homologous arms and cKO region is analyzed to determine the GC content. Significant high GC-content regions are found. It may be difficult to construct this targeting vector. Page 3 of 8 https://www.alphaknockout.com BLAT Search Results (up) QUERY SCORE START END QSIZE IDENTITY CHROM STRAND START END SPAN ----------------------------------------------------------------------------------------------- browser details YourSeq 3000 1 3000 3000 100.0% chr1 - 136227913 136230912 3000 browser details YourSeq 37 1067 1105 3000 100.0% chr10 + 25482166 25482212 47 browser details YourSeq 24 1009 1040 3000 87.5% chr19 - 4212765 4212796 32 Note: The 3000 bp section upstream of Exon 2 is BLAT searched against the genome. No significant similarity is found. BLAT Search Results (down) QUERY SCORE START END QSIZE IDENTITY CHROM STRAND START END SPAN ----------------------------------------------------------------------------------------------- browser details YourSeq 3000 1 3000 3000 100.0% chr1 - 136224264 136227263 3000 browser details YourSeq 25 103 129 3000 88.5% chr8 + 83831043 83831068 26 browser details YourSeq 23 109 131 3000 100.0% chr7 + 115074554 115074576 23 browser details YourSeq 22 109 130 3000 100.0% chr8 + 104796210 104796231 22 browser details YourSeq 22 109 130 3000 100.0% chr5 + 70174206 70174227 22 browser details YourSeq 21 110 130 3000 100.0% chr19 - 36082506 36082526 21 Note: The 3000 bp section downstream of Exon 2 is BLAT searched against the genome. No significant similarity is found. Page 4 of 8 https://www.alphaknockout.com Gene and protein information: Inava innate immunity activator [ Mus musculus (house mouse) ] Gene ID: 67313, updated on 26-Jun-2020 Gene summary Official Symbol Inava provided by MGI Official Full Name innate immunity activator provided by MGI Primary source MGI:MGI:1921579 See related Ensembl:ENSMUSG00000041605 Gene type protein coding RefSeq status VALIDATED Organism Mus musculus Lineage Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus Also known as D1Mgi54; AI586180; 1700034M08Rik; 4933426C09Rik; 5730559C18Rik Expression Biased expression in colon adult (RPKM 37.5), stomach adult (RPKM 18.3) and 11 other tissues See more Orthologs human all Genomic context Location: 1 E4; 1 See Inava in Genome Data Viewer Exon count: 14 Annotation release Status Assembly Chr Location 108.20200622 current GRCm38.p6 (GCF_000001635.26) 1 NC_000067.6 (136213522..136234293, complement) Build 37.2 previous assembly MGSCv37 (GCF_000001635.18) 1 NC_000067.5 (138110108..138130841, complement) Chromosome 1 - NC_000067.6 Page 5 of 8 https://www.alphaknockout.com Transcript information: This gene has 6 transcripts Gene: Inava ENSMUSG00000041605 Description innate immunity activator [Source:MGI Symbol;Acc:MGI:1921579] Gene Synonyms 5730559C18Rik Location Chromosome 1: 136,213,531-136,234,264 reverse strand. GRCm38:CM000994.2 About this gene This gene has 6 transcripts (splice variants), 329 orthologues, 1 paralogue and is a member of 1 Ensembl protein family. Transcripts Name Transcript ID bp Protein Translation ID Biotype CCDS UniProt Flags Inava- ENSMUST00000120339.7 2988 677aa ENSMUSP00000113785.1 Protein coding CCDS15325 G3X9Z8 TSL:1 201 GENCODE basic APPRIS P1 Inava- ENSMUST00000144464.6 811 200aa ENSMUSP00000115554.1 Protein coding - D3YZT8 CDS 3' 202 incomplete TSL:5 Inava- ENSMUST00000150163.7 743 212aa ENSMUSP00000118074.1 Protein coding - D3YZL7 CDS 3' 203 incomplete TSL:3 Inava- ENSMUST00000195177.1 428 78aa ENSMUSP00000141506.1 Protein coding - A0A0A6YWD6 CDS 3' 206 incomplete TSL:3 Inava- ENSMUST00000153910.1 482 97aa ENSMUSP00000120263.1 Nonsense mediated - D6RJ44 TSL:3 204 decay Inava- ENSMUST00000194374.1 2387 No - Retained intron - - TSL:2 205 protein Page 6 of 8 https://www.alphaknockout.com 40.73 kb Forward strand 136.21Mb 136.22Mb 136.23Mb 136.24Mb Genes Gm26568-201 >antisense (Comprehensive set... Contigs AC124550.4 > Genes (Comprehensive set... < Mroh3-205protein coding < Inava-201protein coding < Mroh3-204nonsense mediated decay < Inava-203protein coding < Inava-202protein coding < Inava-205retained intron < Inava-204nonsense mediated decay < Inava-206protein coding Regulatory Build 136.21Mb 136.22Mb 136.23Mb 136.24Mb Reverse strand 40.73 kb Regulation Legend CTCF Open Chromatin Promoter Promoter Flank Gene Legend Protein Coding Ensembl protein coding merged Ensembl/Havana Non-Protein Coding processed transcript Page 7 of 8 https://www.alphaknockout.com Transcript: ENSMUST00000120339 < Inava-201protein coding Reverse strand 20.73 kb ENSMUSP00000113... MobiDB lite Low complexity (Seg) Pfam Domain of unknown function DUF3338 PANTHER PTHR16093 Innate immunity activator protein All sequence SNPs/i... Sequence variants (dbSNP and all other sources) Variant Legend missense variant synonymous variant Scale bar 0 60 120 180 240 300 360 420 480 540 600 677 We wish to acknowledge the following valuable scientific information resources: Ensembl, MGI, NCBI, UCSC. Page 8 of 8.
Load more

Recommended publications
  • Supplementary Information
    Supplementary Information This text file includes: Supplementary Methods Supplementary Figure 1-13, 15-30 Supplementary Table 1-8, 16, 20-21, 23, 25-37, 40-41 1 1. Samples, DNA extraction and genome sequencing 1.1 Ethical statements and sample storage The ethical statements of collecting and processing tissue samples for each species are listed as follows: Myotis myotis: All procedures were carried out in accordance with the ethical guidelines and permits (AREC-13-38-Teeling) delivered by the University College Dublin and the Préfet du Morbihan, awarded to Emma Teeling and Sébastien Puechmaille respectively. A single M. myotis individual was humanely sacrificed given that she had lethal injuries, and dissected. Rhinolophus ferrumequinum: All the procedures were conducted under the license (Natural England 2016-25216-SCI-SCI) issued to Gareth Jones. The individual bat died unexpectedly and suddenly during sampling and was dissected immediately. Pipistrellus kuhlii: The sampling procedure was carried out following all the applicable national guidelines for the care and use of animals. Sampling was done in accordance with all the relevant wildlife legislation and approved by the Ministry of Environment (Ministero della Tutela del Territorio e del Mare, Aut.Prot. N˚: 13040, 26/03/2014). Molossus molossus: All sampling methods were approved by the Ministerio de Ambiente de Panamá (SE/A-29-18) and by the Institutional Animal Care and Use Committee of the Smithsonian Tropical Research Institute (2017-0815-2020). Phyllostomus discolor: P. discolor bats originated from a breeding colony in the Department Biology II of the Ludwig-Maximilians-University in Munich. Approval to keep and breed the bats was issued by the Munich district veterinary office.
    [Show full text]
  • Applying Machine Learning to Breast Cancer Gene Expression Data to Predict Survival Likelihood Pegah Tavangar Thesis Submitted T
    Applying Machine Learning to Breast Cancer Gene Expression Data to Predict Survival Likelihood Pegah Tavangar Thesis submitted to the University of Ottawa in partial Fulfillment of the requirements for the Master of Science in Chemistry and Biomolecular Sciences Department of Chemistry and Biomolecular Sciences Faculty of Science University of Ottawa © Pegah Tavangar, Ottawa, Canada, 2020 Abstract Analyzing the expression level of thousands of genes will provide additional information beneficial in improving cancer therapy or synthesizing a new drug. In this project, the expression of 48807 genes from primary human breast tumors cells was analyzed. Humans cannot make sense of such a large volume of gene expression data from each person. Therefore, we used Machine Learning as an automated system that can learn from the data and be able to predict results from the data. This project presents the use of Machine Learning to predict the likelihood of survival in breast cancer patients using gene expression profiling. Machine Learning techniques, such as Logistic Regression, Support Vector Machines, Random Forest, and different Feature Selection techniques were used to find essential genes that lead to breast cancer or help a patient to live longer. This project describes the evaluation of different Machine Learning algorithms to classify breast cancer tumors into two groups of high and low survival. ii Acknowledgments I would like to thank Dr. Jonathan Lee for providing me the opportunity to work with him on an exciting project. I would like to recognize the invaluable counsel that you all provided during my research. It was my honor to work with some other professors in the Faculty of Medicine, such as Dr.
    [Show full text]
  • Product Datasheet INAVA Overexpression
    Product Datasheet INAVA Overexpression Lysate NBP2-06832 Unit Size: 0.1 mg Store at -80C. Avoid freeze-thaw cycles. Protocols, Publications, Related Products, Reviews, Research Tools and Images at: www.novusbio.com/NBP2-06832 Updated 3/17/2020 v.20.1 Earn rewards for product reviews and publications. Submit a publication at www.novusbio.com/publications Submit a review at www.novusbio.com/reviews/destination/NBP2-06832 Page 1 of 2 v.20.1 Updated 3/17/2020 NBP2-06832 INAVA Overexpression Lysate Product Information Unit Size 0.1 mg Concentration The exact concentration of the protein of interest cannot be determined for overexpression lysates. Please contact technical support for more information. Storage Store at -80C. Avoid freeze-thaw cycles. Buffer RIPA buffer Target Molecular Weight 72.7 kDa Product Description Description Transient overexpression lysate of chromosome 1 open reading frame 106 (C1orf106), transcript variant 1 The lysate was created in HEK293T cells, using Plasmid ID RC215863 and based on accession number NM_018265. The protein contains a C-MYC/DDK Tag. Gene ID 55765 Gene Symbol C1ORF106 Species Human Notes HEK293T cells in 10-cm dishes were transiently transfected with a non-lipid polymer transfection reagent specially designed and manufactured for large volume DNA transfection. Transfected cells were cultured for 48hrs before collection. The cells were lysed in modified RIPA buffer (25mM Tris-HCl pH7.6, 150mM NaCl, 1% NP-40, 1mM EDTA, 1xProteinase inhibitor cocktail mix, 1mM PMSF and 1mM Na3VO4, and then centrifuged to clarify the lysate. Protein concentration was measured by BCA protein assay kit.This product is manufactured by and sold under license from OriGene Technologies and its use is limited solely for research purposes.
    [Show full text]
  • Investigating a Microrna-499-5P Network During Cardiac Development
    Investigating a microRNA-499-5p network during cardiac development Thesis for a PhD degree Submitted to University of East Anglia by Johannes Gottfried Wittig This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with the author and that use of any information derived therefrom must be in accordance with current UK Copyright Law. In addition, any quotation or extract must include full attribution. Principal Investigator: Prof. Andrea Münsterberg Submission Date: 10.05.2019 Declaration of own work Declaration of own work I, Johannes Wittig, confirm that the work for the report with the title: “Investigating a microRNA-499-5p network during cardiac development” was undertaken by myself and that no help was provided from other sources than those allowed. All sections of the report that use quotes or describe an argument or development investigated by other scientist have been referenced, including all secondary literature used, to show that this material has been adopted to support my report. Place/Date Signature II Acknowledgements Acknowledgements I am very happy that I had the chance to be part of the Münsterberg-lab for my PhD research, therefore I would very much like to thank Andrea Münsterberg for offering me this great position in her lab. I especially want to thank her for her patience with me in all the moments where I was impatient and complained about slow progress. I also would like to say thank you for the incredible freedom I had during my PhD work and the support she gave me in the lab but also the understanding for all my non-science related activities.
    [Show full text]
  • INAVA Mouse Monoclonal Antibody [Clone ID: OTI6A6] – TA807187
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA807187 INAVA Mouse Monoclonal Antibody [Clone ID: OTI6A6] Product data: Product Type: Primary Antibodies Clone Name: OTI6A6 Applications: IHC, WB Recommend Dilution: WB 1:2000, IHC 1:150 Reactivity: Human Host: Mouse Isotype: IgG1 Clonality: Monoclonal Immunogen: Human recombinant protein fragment corresponding to amino acids 1-270 of human C1ORF106(NP_060735) produced in E.coli. Formulation: PBS (PH 7.3) containing 1% BSA, 50% glycerol and 0.02% sodium azide. Concentration: 1 mg/ml Purification: Purified from mouse ascites fluids or tissue culture supernatant by affinity chromatography (protein A/G) Predicted Protein Size: 72.7 kDa Gene Name: chromosome 1 open reading frame 106 Database Link: NP_060735 Entrez Gene 55765 Human Synonyms: FLJ10901; MGC125608 This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2020 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 3 INAVA Mouse Monoclonal Antibody [Clone ID: OTI6A6] – TA807187 Product images: HEK293T cells were transfected with the pCMV6- ENTRY control (Left lane) or pCMV6-ENTRY C1orf106 ([RC215863], Right lane) cDNA for 48 hrs and lysed. Equivalent amounts of cell lysates (5 ug per lane) were separated by SDS-PAGE and immunoblotted with anti-C1orf106 (1:2000). Positive lysates [LY413177] (100ug) and [LC413177] (20ug) can be purchased separately from OriGene. Immunohistochemical staining of paraffin- embedded Carcinoma of Human lung tissue using anti-C1orf106 mouse monoclonal antibody.
    [Show full text]
  • Sequencing of Over 100,000 Individuals Identifies Multiple Genes and Rare Variants Associated with Crohns Disease Susceptibility
    medRxiv preprint doi: https://doi.org/10.1101/2021.06.15.21258641; this version posted June 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Sequencing of over 100,000 individuals identifies multiple genes and rare variants associated with Crohns disease susceptibility Aleksejs Sazonovs1*, Christine R. Stevens2,3,4*, Guhan R. Venkataraman5*, Kai Yuan3,4*, Brandon Avila3,6, Maria T. Abreu7, Tariq Ahmad8, Matthieu Allez9, Gil Atzmon10,11, Aris Baras12, Jeffrey C. Barrett13, Nir Barzilai11,14, Laurent Beaugerie15, Ashley Beecham16,17, Charles Bernstein18, Alain Bitton19, Bernd Bokemeyer20, Andrew Chan21, Daniel Chung22, Isabelle Cleynen23, Jacques Cosnes24, David J. Cutler25,26,27, Allan Daly28, Oriana M. Damas7, Lisa W. Datta29, Noor Dawany30, Marcella Devoto30,31,32, Angela Dobes33, Sheila Dodge34, Eva Ellinghaus35, Laura Fachal1, Martti Farkkila36, William Faubion37, Manuel Ferreira12, Denis Franchimont38, Stacey B. Gabriel34, Michel Georges39, Kyle Gettler40, Mamta Giri40, Benjamin Glaser41, Siegfried Goerg42, Philippe Goyette43, Daniel Graham44,45,46, Eija Hämäläinen47, Talin Haritunians48, Graham A. Heap8, Mikko Hiltunen49, Marc Hoeppner50, Julie E. Horowitz51, Peter Irving52,53, Vivek Iyer28, Chaim Jalas54, Judith Kelsen30, Hamed Khalili21, Barbara S. Kirschner55, Kimmo Kontula56, Jukka T. Koskela47, Subra Kugathasan26, Juozas Kupcinskas57, Christopher A. Lamb58,59, Matthias Laudes42, Debby Laukens60, Adam P. Levine61, James Lewis33,62, Claire Liefferinckx38, Britt-Sabina Loescher35, Edouard Louis63, John Mansfield58,59, Sandra May35, Jacob L. McCauley16,17, Emebet Mengesha48, Myriam Mni39, Paul Moayyedi64, Christopher J. Moran22, Rodney Newberry65, Sirimon O’Charoen66, David T.
    [Show full text]
  • A Transcriptome-Wide Isoform Landscape of Melanocytic Nevi and Primary Melanomas Identifies Gene Isoforms Associated with Malignancy
    International Journal of Molecular Sciences Article A Transcriptome-Wide Isoform Landscape of Melanocytic Nevi and Primary Melanomas Identifies Gene Isoforms Associated with Malignancy Siras Hakobyan 1 , Henry Loeffler-Wirth 2, Arsen Arakelyan 1 , Hans Binder 2,† and Manfred Kunz 3,*,† 1 Institute of Molecular Biology NAS RA, Yerevan 0014, Armenia; [email protected] (S.H.); [email protected] (A.A.) 2 Interdisciplinary Centre for Bioinformatics, University of Leipzig, Härtelstr. 16–18, 04107 Leipzig, Germany; [email protected] (H.L.-W.); [email protected] (H.B.) 3 Department of Dermatology, Venereology and Allergology, University of Leipzig Medical Center, Philipp-Rosenthal-Str. 23, 04103 Leipzig, Germany * Correspondence: [email protected]; Tel.: +49-341-9718610; Fax: +49-341-9718609 † Shared senior authorship. Abstract: Genetic splice variants have become of central interest in recent years, as they play an important role in different cancers. Little is known about splice variants in melanoma. Here, we analyzed a genome-wide transcriptomic dataset of benign melanocytic nevi and primary melanomas (n = 80) for the expression of specific splice variants. Using kallisto, a map for differentially expressed splice variants in melanoma vs. benign melanocytic nevi was generated. Among the top genes with differentially expressed splice variants were Ras-related in brain 6B (RAB6B), a member of Citation: Hakobyan, S.; the RAS family of GTPases, Macrophage Scavenger Receptor 1 (MSR1), Collagen Type XI Alpha 2 Loeffler-Wirth, H.; Arakelyan, A.; Chain (COLL11A2), and LY6/PLAUR Domain Containing 1 (LYPD1). The Gene Ontology terms of Binder, H.; Kunz, M. A differentially expressed splice variants showed no enrichment for functional gene sets of melanoma Transcriptome-Wide Isoform vs.
    [Show full text]
  • INAVA Promotes Aggressiveness of Papillary Thyroid Cancer By
    Guan et al. Cell Biosci (2018) 8:26 https://doi.org/10.1186/s13578-018-0224-4 Cell & Bioscience RESEARCH Open Access INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9 expression Hongyu Guan1†, Yan Guo1†, Liehua Liu1†, Runyi Ye2, Weiwei Liang1, Hai Li1, Haipeng Xiao1 and Yanbing Li1* Abstract Background: Innate immunity activator (INAVA) has been shown to be elevated in lung adenocarcinoma. However, its expression pattern and function in papillary thyroid cancer (PTC) are unknown. This study aimed to identify the clinical, biological, and mechanistic impacts of INAVA on PTC. Methods: Using The Cancer Genome Atlas dataset, real time PCR, and immunohistochemistry, the expression of INAVA in PTC was analyzed. Gain- and loss-of-function assays were performed to investigate the role of INAVA in PTC cell invasion, migration, and metastasis. We explored the molecular mechanisms underlying the roles of INAVA in PTC cells using transcriptome resequencing, real time PCR, western blotting and immunohistochemistry. Results: We found that INAVA expression was signifcantly upregulated in PTC and was signifcantly associated with lymph node metastasis. Loss- and gain-of-function experiments demonstrated that INAVA promoted the aggres- sive phenotype of PTC cells in vitro and in vivo. Mechanistic study suggested that upregulation of INAVA resulted in elevated fbroblast growth factor 1 (FGF1), which in turn increased the expression level of matrix metalloproteinases 9 (MMP9). We further identifed that the level of INAVA was positively correlated with the levels of FGF1 and MMP9 in clinical PTC specimens. Conclusion: These data establish a novel role for INAVA in promoting PTC progression and suggest that INAVA may represent a therapeutic target for the disease.
    [Show full text]
  • A Meta-Analysis of the Effects of High-LET Ionizing Radiations in Human Gene Expression
    Supplementary Materials A Meta-Analysis of the Effects of High-LET Ionizing Radiations in Human Gene Expression Table S1. Statistically significant DEGs (Adj. p-value < 0.01) derived from meta-analysis for samples irradiated with high doses of HZE particles, collected 6-24 h post-IR not common with any other meta- analysis group. This meta-analysis group consists of 3 DEG lists obtained from DGEA, using a total of 11 control and 11 irradiated samples [Data Series: E-MTAB-5761 and E-MTAB-5754]. Ensembl ID Gene Symbol Gene Description Up-Regulated Genes ↑ (2425) ENSG00000000938 FGR FGR proto-oncogene, Src family tyrosine kinase ENSG00000001036 FUCA2 alpha-L-fucosidase 2 ENSG00000001084 GCLC glutamate-cysteine ligase catalytic subunit ENSG00000001631 KRIT1 KRIT1 ankyrin repeat containing ENSG00000002079 MYH16 myosin heavy chain 16 pseudogene ENSG00000002587 HS3ST1 heparan sulfate-glucosamine 3-sulfotransferase 1 ENSG00000003056 M6PR mannose-6-phosphate receptor, cation dependent ENSG00000004059 ARF5 ADP ribosylation factor 5 ENSG00000004777 ARHGAP33 Rho GTPase activating protein 33 ENSG00000004799 PDK4 pyruvate dehydrogenase kinase 4 ENSG00000004848 ARX aristaless related homeobox ENSG00000005022 SLC25A5 solute carrier family 25 member 5 ENSG00000005108 THSD7A thrombospondin type 1 domain containing 7A ENSG00000005194 CIAPIN1 cytokine induced apoptosis inhibitor 1 ENSG00000005381 MPO myeloperoxidase ENSG00000005486 RHBDD2 rhomboid domain containing 2 ENSG00000005884 ITGA3 integrin subunit alpha 3 ENSG00000006016 CRLF1 cytokine receptor like
    [Show full text]
  • 1 Resetting Proteostasis with ISRIB Prevents Pulmonary Fibrosis Satoshi Watanabe1,2, Nikolay S. Markov1, Ziyan Lu1, Raul Piseaux
    bioRxiv preprint doi: https://doi.org/10.1101/2020.02.26.965566; this version posted February 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Resetting proteostasis with ISRIB prevents pulmonary fibrosis Satoshi Watanabe1,2, Nikolay S. Markov1, Ziyan Lu1, Raul Piseaux Aillon1, Saul Soberanes1, Constance E. Runyan1, Ziyou Ren1, Rogan A. Grant1, Mariana Maciel1, Hiam Abdala-Valencia1, Yuliya Politanska1, Kiwon Nam1, Lango Sichizya1, Hermon G. Kihshen1, Nikita Joshi1, Alexandra C. McQuattie-Pimentel1, Richard I. Morimoto3, Paul A. Reyfman1, G.R. Scott Budinger1,4, Alexander V. Misharin1,4 1Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA 2Department of Respiratory Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, 920-8641, Japan 3Deparment of Molecular Biosciences, Northwestern University, Evanston, IL 60208 4These senior authors contributed equally Running title: ISRIB ameliorates pulmonary fibrosis in aging Corresponding author: G.R. Scott Budinger Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine 303 E Superior, Simpson Querrey Biomedical Research Center, 5th floor, Chicago, IL, 60611, USA E-mail: [email protected] Phone: 312-908-7737, Fax: 312-503-0411 Alexander V. Misharin Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine 303 E Superior, Simpson Querrey Biomedical Research Center , 5th floor, Chicago, IL, 60611, USA E-mail: [email protected] Phone: 312-908-7737, Fax: 312-503-0411 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.02.26.965566; this version posted February 27, 2020.
    [Show full text]
  • Sequencing of Over 100,000 Individuals Identifies Multiple Genes and Rare Variants Associated with Crohns Disease Susceptibility
    medRxiv preprint doi: https://doi.org/10.1101/2021.06.15.21258641; this version posted July 5, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Sequencing of over 100,000 individuals identifies multiple genes and rare variants associated with Crohns disease susceptibility Aleksejs Sazonovs1*, Christine R. Stevens2,3,4*, Guhan R. Venkataraman5*, Kai Yuan3,4*, Brandon Avila3,6, Maria T. Abreu7, Tariq Ahmad8, Matthieu Allez9, Ashwin N. Ananthakrishnan 10, Gil Atzmon11,12, Aris Baras13, Jeffrey C. Barrett14, Nir Barzilai12,15, Laurent Beaugerie16, Ashley Beecham17,18, Charles N. Bernstein19, Alain Bitton20, Bernd Bokemeyer21, Andrew Chan22,23, Daniel Chung24, Isabelle Cleynen25, Jacques Cosnes26, David J. Cutler27,28,29, Allan Daly30, Oriana M. Damas31, Lisa W. Datta32, Noor Dawany33, Marcella Devoto33,34,35, Sheila Dodge36, Eva Ellinghaus37, Laura Fachal1, Martti Farkkila38, William Faubion39, Manuel Ferreira13, Denis Franchimont40, Stacey B. Gabriel36, Michel Georges41, Kyle Gettler42, Mamta Giri42, Benjamin Glaser43, Siegfried Goerg44, Philippe Goyette45, Daniel Graham46,47,48, Eija Hämäläinen49, Talin Haritunians50, Graham A. Heap8, Mikko Hiltunen51, Marc Hoeppner52, Julie E. Horowitz53, Peter Irving54,55, Vivek Iyer30, Chaim Jalas56, Judith Kelsen33, Hamed Khalili22, Barbara S. Kirschner57, Kimmo Kontula58, Jukka T. Koskela49, Subra Kugathasan28, Juozas Kupcinskas59, Christopher A. Lamb60,61, Matthias Laudes44, Adam P. Levine62, James Lewis63,64, Claire Liefferinckx40, Britt-Sabina Loescher37, Edouard Louis65, John Mansfield60,61, Sandra May37, Jacob L. McCauley17,18, Emebet Mengesha50, Myriam Mni41, Paul Moayyedi66, Christopher J.
    [Show full text]
  • An Inflammatory Bowel Disease–Risk Variant in INAVA Decreases Pattern Recognition Receptor–Induced Outcomes
    RESEARCH ARTICLE The Journal of Clinical Investigation An inflammatory bowel disease–risk variant in INAVA decreases pattern recognition receptor–induced outcomes Jie Yan, Matija Hedl, and Clara Abraham Department of Medicine, Yale University, New Haven, Connecticut, USA. Inflammatory bowel disease (IBD) is characterized by dysregulation in both cytokines and responses to intestinal microbes, and proper regulation of pattern recognition receptor (PRR) signaling is critical for intestinal immune homeostasis. Altered functions for the IBD risk locus containing rs7554511, which encompasses the C1orf106 gene (recently named INAVA), and roles for the protein encoded by the INAVA gene are unknown. Here, we investigated the role of INAVA and INAVA genotype in regulating PRR-initiated outcomes in primary human cells. Both peripheral and intestinal myeloid cells expressed INAVA. Upon PRR stimulation, INAVA was required for optimal MAPK and NF-κB activation, cytokine secretion, and intracellular bacterial clearance. INAVA recruited 14-3-3τ, thereby contributing to recruitment of a signaling complex that amplified downstream signals and cytokines. Further, INAVA enhanced bacterial clearance by regulating reactive oxygen, reactive nitrogen, and autophagy pathways. Macrophages from rs7554511 C risk carriers expressed lower levels of INAVA RNA and protein. Lower expression was attributed in part to decreased transcription mediated directly by the intronic region containing the rs7554511 C variant. In rs7554511 C risk carrier macrophages, lower INAVA
    [Show full text]