Mouse Ttc39a Knockout Project (CRISPR/Cas9)
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Number 2 February 2014
Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL INIST -CNRS Volume 18 - Number 2 February 2014 The PDF version of the Atlas of Genetics and Cytogenetics in Oncology and Haematology is a reissue of the original articles published in collaboration with the Institute for Scientific and Technical Information (INstitut de l’Information Scientifique et Technique - INIST) of the French National Center for Scientific Research (CNRS) on its electronic publishing platform I-Revues. Online and PDF versions of the Atlas of Genetics and Cytogenetics in Oncology and Haematology are hosted by INIST-CNRS. Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL INIST -CNRS Scope The Atlas of Genetics and Cytogenetics in Oncology and Haematology is a peer reviewed on-line journal in open access, devoted to genes, cytogenetics, and clinical entities in cancer, and cancer-prone diseases. It presents structured review articles (“cards”) on genes, leukaemias, solid tumours, cancer-prone diseases, and also more traditional review articles (“deep insights”) on the above subjects and on surrounding topics. It also present case reports in hematology and educational items in the various related topics for students in Medicine and in Sciences. Editorial correspondance Jean-Loup Huret Genetics, Department of Medical Information, University Hospital F-86021 Poitiers, France tel +33 5 49 44 45 46 or +33 5 49 45 47 67 [email protected] or [email protected] Staff Mohammad Ahmad, Mélanie Arsaban, Marie-Christine Jacquemot-Perbal, Vanessa Le Berre, Anne Malo, Carol Moreau, Catherine Morel-Pair, Laurent Rassinoux, Alain Zasadzinski. Philippe Dessen is the Database Director, and Alain Bernheim the Chairman of the on-line version (Gustave Roussy Institute – Villejuif – France). -
Cellular and Molecular Signatures in the Disease Tissue of Early
Cellular and Molecular Signatures in the Disease Tissue of Early Rheumatoid Arthritis Stratify Clinical Response to csDMARD-Therapy and Predict Radiographic Progression Frances Humby1,* Myles Lewis1,* Nandhini Ramamoorthi2, Jason Hackney3, Michael Barnes1, Michele Bombardieri1, Francesca Setiadi2, Stephen Kelly1, Fabiola Bene1, Maria di Cicco1, Sudeh Riahi1, Vidalba Rocher-Ros1, Nora Ng1, Ilias Lazorou1, Rebecca E. Hands1, Desiree van der Heijde4, Robert Landewé5, Annette van der Helm-van Mil4, Alberto Cauli6, Iain B. McInnes7, Christopher D. Buckley8, Ernest Choy9, Peter Taylor10, Michael J. Townsend2 & Costantino Pitzalis1 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Departments of 2Biomarker Discovery OMNI, 3Bioinformatics and Computational Biology, Genentech Research and Early Development, South San Francisco, California 94080 USA 4Department of Rheumatology, Leiden University Medical Center, The Netherlands 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 6Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Cagliari, Italy 7Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 8Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham B15 2WB, UK 9Institute of -
Supp Table 6.Pdf
Supplementary Table 6. Processes associated to the 2037 SCL candidate target genes ID Symbol Entrez Gene Name Process NM_178114 AMIGO2 adhesion molecule with Ig-like domain 2 adhesion NM_033474 ARVCF armadillo repeat gene deletes in velocardiofacial syndrome adhesion NM_027060 BTBD9 BTB (POZ) domain containing 9 adhesion NM_001039149 CD226 CD226 molecule adhesion NM_010581 CD47 CD47 molecule adhesion NM_023370 CDH23 cadherin-like 23 adhesion NM_207298 CERCAM cerebral endothelial cell adhesion molecule adhesion NM_021719 CLDN15 claudin 15 adhesion NM_009902 CLDN3 claudin 3 adhesion NM_008779 CNTN3 contactin 3 (plasmacytoma associated) adhesion NM_015734 COL5A1 collagen, type V, alpha 1 adhesion NM_007803 CTTN cortactin adhesion NM_009142 CX3CL1 chemokine (C-X3-C motif) ligand 1 adhesion NM_031174 DSCAM Down syndrome cell adhesion molecule adhesion NM_145158 EMILIN2 elastin microfibril interfacer 2 adhesion NM_001081286 FAT1 FAT tumor suppressor homolog 1 (Drosophila) adhesion NM_001080814 FAT3 FAT tumor suppressor homolog 3 (Drosophila) adhesion NM_153795 FERMT3 fermitin family homolog 3 (Drosophila) adhesion NM_010494 ICAM2 intercellular adhesion molecule 2 adhesion NM_023892 ICAM4 (includes EG:3386) intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)adhesion NM_001001979 MEGF10 multiple EGF-like-domains 10 adhesion NM_172522 MEGF11 multiple EGF-like-domains 11 adhesion NM_010739 MUC13 mucin 13, cell surface associated adhesion NM_013610 NINJ1 ninjurin 1 adhesion NM_016718 NINJ2 ninjurin 2 adhesion NM_172932 NLGN3 neuroligin -
Mouse Ttc39a Conditional Knockout Project (CRISPR/Cas9)
https://www.alphaknockout.com Mouse Ttc39a Conditional Knockout Project (CRISPR/Cas9) Objective: To create a Ttc39a conditional knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Ttc39a gene (NCBI Reference Sequence: NM_153392 ; Ensembl: ENSMUSG00000028555 ) is located on Mouse chromosome 4. 18 exons are identified, with the ATG start codon in exon 1 and the TAG stop codon in exon 18 (Transcript: ENSMUST00000064129). Exon 3~5 will be selected as conditional knockout region (cKO region). Deletion of this region should result in the loss of function of the Mouse Ttc39a gene. To engineer the targeting vector, homologous arms and cKO region will be generated by PCR using BAC clone RP23-110F24 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 3 starts from about 8.33% of the coding region. The knockout of Exon 3~5 will result in frameshift of the gene. The size of intron 2 for 5'-loxP site insertion: 5201 bp, and the size of intron 5 for 3'-loxP site insertion: 3358 bp. The size of effective cKO region: ~2297 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 5' gRNA region gRNA region 3' 1 3 4 5 18 Targeting vector Targeted allele Constitutive KO allele (After Cre recombination) Legends Exon of mouse Ttc39a 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. -
Genetic Characterization of Large Parathyroid Adenomas
Endocrine-Related Cancer (2012) 19 389–407 Genetic characterization of large parathyroid adenomas Luqman Sulaiman1,2, Inga-Lena Nilsson3, C Christofer Juhlin1,2,4, Felix Haglund1,2, Anders Ho¨o¨g4, Catharina Larsson1,2 and Jamileh Hashemi1,2 1Medical Genetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital CMM L8:01, SE-171 76 Stockholm, Sweden 2Center for Molecular Medicine, Karolinska University Hospital, L8:01, SE-171 76 Stockholm, Sweden 3Endocrine Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital P9:03, SE-171 76 Stockholm, Sweden 4Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital P1:02, SE-171 76 Stockholm, Sweden (Correspondence should be addressed to C Larsson at Medical Genetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital CMM L8:01; Email: [email protected]) Abstract In this study, we genetically characterized parathyroid adenomas with large glandular weights, for which independent observations suggest pronounced clinical manifestations. Large parathyroid adenomas (LPTAs) were defined as the 5% largest sporadic parathyroid adenomas identified among the 590 cases operated in our institution during 2005–2009. The LPTA group showed a higher relative number of male cases and significantly higher levels of total plasma and ionized serum calcium (P!0.001). Further analysis of 21 LPTAs revealed low MIB1 proliferation index (0.1–1.5%), MEN1 mutations in five cases, and one HRPT2 (CDC73) mutation. Total or partial loss of parafibromin expression was observed in ten tumors, two of which also showed loss of APC expression. -
The Link Between Type 2 Diabetes Mellitus and the Polymorphisms Of
life Article The Link between Type 2 Diabetes Mellitus and the Polymorphisms of Glutathione-Metabolizing Genes Suggests a New Hypothesis Explaining Disease Initiation and Progression Iuliia Azarova 1,2 , Elena Klyosova 2 and Alexey Polonikov 3,4,* 1 Department of Biological Chemistry, Kursk State Medical University, 3 Karl Marx Street, 305041 Kursk, Russia; [email protected] 2 Laboratory of Biochemical Genetics and Metabolomics, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 18 Yamskaya St., 305041 Kursk, Russia; [email protected] 3 Laboratory of Statistical Genetics and Bioinformatics, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 18 Yamskaya St., 305041 Kursk, Russia 4 Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, 305041 Kursk, Russia * Correspondence: [email protected]; Tel.: +7-471-258-8147 Abstract: The present study investigated whether type 2 diabetes (T2D) is associated with polymor- phisms of genes encoding glutathione-metabolizing enzymes such as glutathione synthetase (GSS) and gamma-glutamyl transferase 7 (GGT7). A total of 3198 unrelated Russian subjects including 1572 T2D patients and 1626 healthy subjects were enrolled. Single nucleotide polymorphisms (SNPs) of the GSS and GGT7 genes were genotyped using the MassArray-4 system. We found that the GSS Citation: Azarova, I.; Klyosova, E.; and GGT7 gene polymorphisms alone and in combinations are associated with T2D risk regardless of Polonikov, A. The Link between Type sex, age, and body mass index, as well as correlated with plasma glutathione, hydrogen peroxide, 2 Diabetes Mellitus and the and fasting blood glucose levels. Polymorphisms of GSS (rs13041792) and GGT7 (rs6119534 and Polymorphisms of Glutathione- Metabolizing Genes Suggests a New rs11546155) genes were associated with the tissue-specific expression of genes involved in unfolded Hypothesis Explaining Disease protein response and the regulation of proteostasis. -
Pathways of NF-Κb Activation
Biochemical Journal (2021) 478 2619–2664 https://doi.org/10.1042/BCJ20210139 Review Article Inhibitory feedback control of NF-κB signalling in health and disease Jack A. Prescott*, Jennifer P. Mitchell and Simon J. Cook Signalling Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, U.K. Correspondence: Simon Cook ([email protected]) or Jennifer Mitchell ( [email protected]) Cells must adapt to changes in their environment to maintain cell, tissue and organismal integrity in the face of mechanical, chemical or microbiological stress. Nuclear factor-κB (NF-κB) is one of the most important transcription factors that controls inducible gene expression as cells attempt to restore homeostasis. It plays critical roles in the immune system, from acute inflammation to the development of secondary lymphoid organs, and also has roles in cell survival, proliferation and differentiation. Given its role in such critical processes, NF-κB signalling must be subject to strict spatiotemporal control to ensure measured and context-specific cellular responses. Indeed, deregulation of NF-κB signal- ling can result in debilitating and even lethal inflammation and also underpins some forms of cancer. In this review, we describe the homeostatic feedback mechanisms that limit and ‘re-set’ inducible activation of NF-κB. We first describe the key components of the signalling pathways leading to activation of NF-κB, including the prominent role of protein phosphorylation and protein ubiquitylation, before briefly introducing the key fea- tures of feedback control mechanisms. We then describe the array of negative feedback loops targeting different components of the NF-κB signalling cascade including controls at the receptor level, post-receptor signalosome complexes, direct regulation of the crit- ical ‘inhibitor of κB kinases’ (IKKs) and inhibitory feedforward regulation of NF-κB- dependent transcriptional responses. -
Gene Expression During the Generation and Activation of Mouse Neutrophils: Implication of Novel Functional and Regulatory Pathways
Gene Expression during the Generation and Activation of Mouse Neutrophils: Implication of Novel Functional and Regulatory Pathways Jeffrey A. Ericson1, Pierre Duffau2, Kei Yasuda2, Adriana Ortiz-Lopez1, Katherine Rothamel1, Ian R. Rifkin2, Paul A. Monach2*, ImmGen Consortium" 1 Division of Immunology, Department of Microbiology and Immunology, Harvard Medical School, Boston, MA, United States of America, 2 Department of Medicine, Boston University School of Medicine, Boston, MA, United States of America Abstract As part of the Immunological Genome Project (ImmGen), gene expression was determined in unstimulated (circulating) mouse neutrophils and three populations of neutrophils activated in vivo, with comparison among these populations and to other leukocytes. Activation conditions included serum-transfer arthritis (mediated by immune complexes), thioglycollate-induced peritonitis, and uric acid-induced peritonitis. Neutrophils expressed fewer genes than any other leukocyte population studied in ImmGen, and down-regulation of genes related to translation was particularly striking. However, genes with expression relatively specific to neutrophils were also identified, particularly three genes of unknown function: Stfa2l1, Mrgpr2a and Mrgpr2b. Comparison of genes up-regulated in activated neutrophils led to several novel findings: increased expression of genes related to synthesis and use of glutathione and of genes related to uptake and metabolism of modified lipoproteins, particularly in neutrophils elicited by thioglycollate; increased expression of genes for transcription factors in the Nr4a family, only in neutrophils elicited by serum-transfer arthritis; and increased expression of genes important in synthesis of prostaglandins and response to leukotrienes, particularly in neutrophils elicited by uric acid. Up-regulation of genes related to apoptosis, response to microbial products, NFkB family members and their regulators, and MHC class II expression was also seen, in agreement with previous studies. -
(Passenger Strand of Mir-99A-Duplex) in Head and Neck Squamous Cell Carcinoma
cells Article Regulation of Oncogenic Targets by miR-99a-3p (Passenger Strand of miR-99a-Duplex) in Head and Neck Squamous Cell Carcinoma 1, 1,2, 1 3 Reona Okada y, Keiichi Koshizuka y, Yasutaka Yamada , Shogo Moriya , Naoko Kikkawa 1,2, Takashi Kinoshita 2, Toyoyuki Hanazawa 2 and Naohiko Seki 1,* 1 Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan; [email protected] (R.O.); [email protected] (K.K.); [email protected] (Y.Y.); [email protected] (N.K.) 2 Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan; [email protected] (T.K.); [email protected] (T.H.) 3 Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-43-226-2971; Fax: +81-43-227-3442 These authors contributed equally to this work. y Received: 3 November 2019; Accepted: 27 November 2019; Published: 28 November 2019 Abstract: To identify novel oncogenic targets in head and neck squamous cell carcinoma (HNSCC), we have analyzed antitumor microRNAs (miRNAs) and their controlled molecular networks in HNSCC cells. Based on our miRNA signature in HNSCC, both strands of the miR-99a-duplex (miR-99a-5p: the guide strand, and miR-99a-3p: the passenger strand) are downregulated in cancer tissues. Moreover, low expression of miR-99a-5p and miR-99a-3p significantly predicts poor prognosis in HNSCC, and these miRNAs regulate cancer cell migration and invasion. -
The Functional Role of SEC23 in Vesicle Transportation, Autophagy and Cancer Jingchen Jing1, 2, Bo Wang1, 2, Peijun Liu1, 2
Int. J. Biol. Sci. 2019, Vol. 15 2419 Ivyspring International Publisher International Journal of Biological Sciences 2019; 15 (11): 2419-2426. doi: 10.7150/ijbs.37008 Review The Functional Role of SEC23 in Vesicle Transportation, Autophagy and Cancer Jingchen Jing1, 2, Bo Wang1, 2, Peijun Liu1, 2 1. Center for Translational Medicine, The First Affiliated Hospital, Xi'an Jiaotong University 2. The Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China Corresponding author: Dr. Peijun Liu, Center for Translational Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi 710061, China. E‑mail: [email protected] © The author (s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. Received: 2019.05.26; Accepted: 2019.08.01; Published: 2019.09.07 Abstract SEC23, the core component of the coat protein complex II (COPII), functions to transport newly synthesized proteins and lipids from the endoplasmic reticulum (ER) to the Golgi apparatus in cells for secretion. SEC23 protein has two isoforms (SEC23A and SEC23B) and their aberrant expression and mutations were reported to cause human diseases and oncogenesis, whereas SEC23A and SEC23B may have the opposite activity in human cancer, for a reason that remains unclear. This review summarizes recent research in SEC23, COPII-vesicle transportation, autophagy, and cancer. Key words: SEC23, COPII-vesicle transportation, autophagy, cancer Introduction SEC23 is one of the components in the coat SEC23, COPII-vesicle transportation, autophagy, and protein complex II (COPII) and regulates the cancer development and progression (Fig. -
Autocrine IFN Signaling Inducing Profibrotic Fibroblast Responses By
Downloaded from http://www.jimmunol.org/ by guest on September 23, 2021 Inducing is online at: average * The Journal of Immunology , 11 of which you can access for free at: 2013; 191:2956-2966; Prepublished online 16 from submission to initial decision 4 weeks from acceptance to publication August 2013; doi: 10.4049/jimmunol.1300376 http://www.jimmunol.org/content/191/6/2956 A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Autocrine IFN Signaling Feng Fang, Kohtaro Ooka, Xiaoyong Sun, Ruchi Shah, Swati Bhattacharyya, Jun Wei and John Varga J Immunol cites 49 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2013/08/20/jimmunol.130037 6.DC1 This article http://www.jimmunol.org/content/191/6/2956.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 23, 2021. The Journal of Immunology A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Inducing Autocrine IFN Signaling Feng Fang,* Kohtaro Ooka,* Xiaoyong Sun,† Ruchi Shah,* Swati Bhattacharyya,* Jun Wei,* and John Varga* Activation of TLR3 by exogenous microbial ligands or endogenous injury-associated ligands leads to production of type I IFN. -
Identification of Gene 3 Ends by Automated EST Cluster Analysis
Identification of gene 3 ends by automated EST cluster analysis Enrique M. Muroa,b, Robert Herringtonc, Salima Janmohamedc, Catherine Frelinc, Miguel A. Andrade-Navarroa,b,1, and Norman N. Iscovec,1,2 aOttawa Health Research Institute, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6; bMax Delbru¨ck Center for Molecular Medicine, Robert-Ro¨ssle-Strasse 10, 13125 Berlin, Germany; and cOntario Cancer Institute, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto Medical Discovery Tower, 101 College Street, Toronto, ON, Canada M5G 1L7 Edited by Tak Wah Mak, University of Toronto, Toronto, ON, Canada, and approved October 14, 2008 (received for review August 11, 2008) The properties and biology of mRNA transcripts can be affected abundance of terminal 3Ј sequences. Amplified cDNAs are profoundly by the choice of alternative polyadenylation sites, therefore ideally interrogated by probes that target sequences as .making definition of the 3 ends of transcripts essential for under- close to 3Ј ends as is practical standing their regulation. Here we show that 22–52% of sequences For access to 3Ј terminal sequences, biologists usually turn in commonly used human and murine ‘‘full-length’’ transcript to highly curated collections of complete mRNA sequences, databases may not currently end at bona fide polyadenylation such as the RefSeq (10), Ensembl (11), UCSC KnownGene sites. To identify probable transcript termini over the entire murine (12), FANTOM (3) and VEGA (13) collections. Probes in and human genomes, we analyzed the EST databases for positional widely used commercial microarrays are similarly selected clustering of EST ends. The analysis yielded 58,282 murine- and from sequence collections representative of full-length tran- 86,410 human-candidate polyadenylation sites, of which 75% scripts, from which probes near 3Ј polyadenylation sites could mapped to 23,091 known murine transcripts and 22,891 known be generated in principle.