A SNP in the immunoregulatory molecule CTLA-4 controls mRNA splicing in vivo but does not alter diabetes susceptibility in the NOD mouse

Diabetes

Volumn 65, Issue 1, 2016, Pages 120-128

  Jakubczik, Fabian ^a   Jones, Ken ^a   Nichols, Jennifer ^a   Mansfield, William ^a   Cooke, Anne ^a   Holmes, Nick ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOPHOSPHAMIDE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; MESSENGER RNA; T LYMPHOCYTE RECEPTOR; CTLA4 PROTEIN, MOUSE; ISOPROTEIN;

ADOPTIVE TRANSFER; ALTERNATIVE RNA SPLICING; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLASTOCYST; CD4+ T LYMPHOCYTE; CELL PROLIFERATION; CELL SELECTION; CONTROLLED STUDY; DIABETES MELLITUS; EMBRYO; EMBRYONIC STEM CELL; EXON; FEMALE; GENETIC VARIABILITY; GENOME; HETEROZYGOTE; IMMUNOREGULATION; LOXP SITE; MALE; MOUSE; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; SINGLE NUCLEOTIDE POLYMORPHISM; T LYMPHOCYTE ACTIVATION; ANIMAL; AUTOIMMUNITY; GENE TARGETING; GENETIC PREDISPOSITION; GENETICS; IMMUNOLOGY; INSULIN DEPENDENT DIABETES MELLITUS; METABOLISM; MOUSE EMBRYONIC STEM CELL; NONOBESE DIABETIC MOUSE; RNA SPLICING; TRANSGENIC MOUSE;

ADOPTIVE TRANSFER; ANIMALS; AUTOIMMUNITY; CD4-POSITIVE T-LYMPHOCYTES; CTLA-4 ANTIGEN; DIABETES MELLITUS, TYPE 1; GENE KNOCK-IN TECHNIQUES; GENETIC PREDISPOSITION TO DISEASE; MICE; MICE, INBRED NOD; MICE, TRANSGENIC; MOUSE EMBRYONIC STEM CELLS; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEIN ISOFORMS; RNA SPLICING; RNA, MESSENGER;

EID: 84962159733     PISSN: 00121797     EISSN: 1939327X     Source Type: Journal    
DOI: 10.2337/db15-1175     Document Type: Article

References (22)

1. Burren OS, Adlem EC, Achuthan P, Christensen M, Coulson RM, Todd JA. T1DBase: update 2011, organization and presentation of large-scale data sets for type 1 diabetes research. Nucleic Acids Res 2011;39:D997-D1001
2. Ueda H, Howson JM, Esposito L, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003;423:506-511
3. Catchpole B, Adams JP, Holder AL, Short AD, Ollier WE, Kennedy LJ. Genetics of canine diabetes mellitus: are the diabetes susceptibility genes identified in humans involved in breed susceptibility to diabetes mellitus in dogs? Vet J 2013;195:139-147
4. Wing K, Onishi Y, Prieto-Martin P, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science 2008;322:271-275
5. Hou TZ, Qureshi OS, Wang CJ, et al. A transendocytosis model of CTLA-4 function predicts its suppressive behavior on regulatory T cells. J Immunol 2015; 194:2148-2159
6. Jain N, Nguyen H, Chambers C, Kang J. Dual function of CTLA-4 in regulatory T cells and conventional T cells to prevent multiorgan autoimmunity. Proc Natl Acad Sci U S A 2010;107:1524-1528
7. Wang CJ, Kenefeck R, Wardzinski L, et al. Cutting edge: cell-extrinsic immune regulation by CTLA-4 expressed on conventional T cells. J Immunol 2012;189:1118-1122
8. Vijayakrishnan L, Slavik JM, Illés Z, et al. An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells. Immunity 2004;20:563-575
9. Wicker LS, Chamberlain G, Hunter K, et al. Fine mapping, gene content, comparative sequencing, and expression analyses support Ctla4 and Nramp1 as candidates for Idd5.1 and Idd5.2 in the nonobese diabetic mouse. J Immunol 2004;173:164-173
10. Araki M, Chung D, Liu S, et al. Genetic evidence that the differential expression of the ligand-independent isoform of CTLA-4 is the molecular basis of the Idd5.1 type 1 diabetes region in nonobese diabetic mice. J Immunol 2009; 183:5146-5157
11. Bour-Jordan H, Esensten JH, Martinez-Llordella M, Penaranda C, Stumpf M, Bluestone JA. Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/B7 family. Immunol Rev 2011;241:180-205
12. Jeker LT, Bour-Jordan H, Bluestone JA. Breakdown in peripheral tolerance in type 1 diabetes in mice and humans. Cold Spring Harb Perspect Med 2012;2: a007807
13. Lin X, Hamilton-Williams EE, Rainbow DB, et al. Genetic interactions among Idd3, Idd5.1, Idd5.2, and Idd5.3 protective loci in the nonobese diabetic mouse model of type 1 diabetes. J Immunol 2013;190:3109-3120
14. Nichols J, Jones K, Phillips JM, et al. Validated germline-competent embryonic stem cell lines from nonobese diabetic mice. Nat Med 2009;15:814-818
15. Brode S, Raine T, Zaccone P, Cooke A. Cyclophosphamide-induced type-1 diabetes in the NOD mouse is associated with a reduction of CD4+CD25+Foxp3+ regulatory T cells. J Immunol 2006;177:6603-6612
16. Ikezawa Y, Nakazawa M, Tamura C, Takahashi K, Minami M, Ikezawa Z. Cyclophosphamide decreases the number, percentage and the function of CD25+ CD4+ regulatory T cells, which suppress induction of contact hyper-sensitivity. J Dermatol Sci 2005;39:105-112
17. Stumpf M, Zhou X, Bluestone JA. The B7-independent isoform of CTLA-4 functions to regulate autoimmune diabetes. J Immunol 2013;190: 961-969
18. Haskins K, McDuffie M. Acceleration of diabetes in young NOD mice with a CD4+ islet-specific T cell clone. Science 1990;249:1433-1436
19. Höglund P, Mintern J, Waltzinger C, Heath W, Benoist C, Mathis D. Initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodes. J Exp Med 1999;189:331-339
20. Thomas DC, Mellanby RJ, Phillips JM, Cooke A. An early age-related increase in the frequency of CD4+ Foxp3+ cells in BDC2.5NOD mice. Immunology 2007;121:565-576
21. de Boer J, Williams A, Skavdis G, et al. Transgenic mice with hematopoietic and lymphoid specific expression of Cre. Eur J Immunol 2003;33:314-325
22. Holmes N, Cooke A. Genetic analysis of type 1 diabetes: embryonic stem cells as new tools to unlock biological mechanisms in type 1 diabetes. Rev Diabet Stud 2012;9:137-147