Genetic interactions among Idd3, Idd5.1, Idd5.2, and Idd5.3 protective loci in the nonobese diabetic mouse model of type 1 diabetes

Journal of Immunology

Volumn 190, Issue 7, 2013, Pages 3109-3120

  Lin, Xiaotian ^a   Hamilton Williams, Emma E ^a,e   Rainbow, Daniel B ^b   Hunter, Kara M ^b   Dai, Yang D ^c   Cheung, Jocelyn ^a   Peterson, Laurence B ^d   Wicker, Linda S ^b   Sherman, Linda A ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c TORREY PINES INSTITUTE FOR MOLECULAR STUDIES   (United States)

^d MERCK RESEARCH LABORATORIES   (United States)

^e UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ACADL GENE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; CTLA4 GENE; FEMALE; GENE; GENE INTERACTION; GENE LOCUS; GENE SILENCING; IDD3 GENE; IDD5.1 GENE; IDD5.2 GENE; IDD5.3 GENE; IL2 GENE; IMMUNOLOGICAL TOLERANCE; INSULIN DEPENDENT DIABETES MELLITUS; LOSS OF FUNCTION MUTATION; MOUSE; NONHUMAN; NONOBESE DIABETIC MOUSE; PRIORITY JOURNAL; SCID MOUSE; SLC11A1 GENE;

ALLELES; ANIMALS; CATION TRANSPORT PROTEINS; DIABETES MELLITUS, TYPE 1; EPISTASIS, GENETIC; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GLUCOSE-6-PHOSPHATASE; IMMUNE TOLERANCE; ISLETS OF LANGERHANS; MICE; MICE, INBRED NOD; MICE, SCID; PROTEINS; QUANTITATIVE TRAIT LOCI;

EID: 84875445136     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1203422     Document Type: Article

References (67)

1. Kikutani, H., and S. Makino. 1992. The murine autoimmune diabetes model: NOD and related strains. Adv. Immunol. 51: 285-322.
2. Ghosh, S., S. M. Palmer, N. R. Rodrigues, H. J. Cordell, C. M. Hearne, R. J. Cornall, J. B. Prins, P. McShane, G. M. Lathrop, L. B. Peterson, et al. 1993. Polygenic control of autoimmune diabetes in nonobese diabetic mice. Nat. Genet. 4: 404-409.
3. Ridgway, W. M., L. B. Peterson, J. A. Todd, D. B. Rainbow, B. Healy, O. S. Burren, and L. S. Wicker. 2008. Gene-gene interactions in the NOD mouse model of type 1 diabetes. Adv. Immunol. 100: 151-175.
4. Maier, L. M., and L. S. Wicker. 2005. Genetic susceptibility to type 1 diabetes. Curr. Opin. Immunol. 17: 601-608.
5. Wellcome Trust Case Control Consortium. 2007. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447: 661-678.
6. Manolio, T. A., L. D. Brooks, and F. S. Collins. 2008. A HapMap harvest of insights into the genetics of common disease. J. Clin. Invest. 118: 1590-1605.
7. Barrett, J. C., D. G. Clayton, P. Concannon, B. Akolkar, J. D. Cooper, H. A. Erlich, C. Julier, G. Morahan, J. Nerup, C. Nierras, et al; Type 1 Diabetes Genetics Consortium. 2009. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat. Genet. 41: 703-707.
8. Cooper, J. D., J. M. Howson, D. Smyth, N. M. Walker, H. Stevens, J. H. Yang, J. X. She, G. S. Eisenbarth, M. Rewers, J. A. Todd, et al; Type 1 Diabetes Genetics Consortium. 2012. Confirmation of novel type 1 diabetes risk loci in families. Diabetologia 55: 996-1000.
9. Wicker, L. S., J. Clark, H. I. Fraser, V. E. Garner, A. Gonzalez-Munoz, B. Healy, S. Howlett, K. Hunter, D. Rainbow, R. L. Rosa, et al. 2005. Type 1 diabetes genes and pathways shared by humans and NOD mice. J. Autoimmun. 25: 29-33.
10. Yang, J. H., K. Downes, J. M. Howson, S. Nutland, H. E. Stevens, N. M. Walker, and J. A. Todd. 2011. Evidence of association with type 1 diabetes in the SLC11A1 gene region. BMC Med. Genet. 12: 59.
11. Rainbow, D. B., L. Esposito, S. K. Howlett, K. M. Hunter, J. A. Todd, L. B. Peterson, and L. S. Wicker. 2008. Commonality in the genetic control of type 1 diabetes in humans and NOD mice: variants of genes in the IL-2 pathway are associated with autoimmune diabetes in both species. Biochem. Soc. Trans. 36: 312-315.
12. Wang, J., L. S. Wicker, and P. Santamaria. 2009. IL-2 and its high-affinity receptor: genetic control of immunoregulation and autoimmunity. Semin. Immunol. 21: 363-371.
13. Howson, J. M., J. D. Cooper, D. J. Smyth, N. M. Walker, H. Stevens, J. X. She, G. S. Eisenbarth, M. Rewers, J. A. Todd, B. Akolkar, et al. 2012. Evidence of gene-gene interaction and age-at-diagnosis effects in type 1 diabetes. Diabetes 61: 3012-3017.
14. Podolin, P. L., P. Denny, N. Armitage, C. J. Lord, N. J. Hill, E. R. Levy, L. B. Peterson, J. A. Todd, L. S. Wicker, and P. A. Lyons. 1998. Localization of two insulin-dependent diabetes (Idd) genes to the Idd10 region on mouse chromosome 3. Mamm. Genome 9: 283-286.
15. Hill, N. J., P. A. Lyons, N. Armitage, J. A. Todd, L. S. Wicker, and L. B. Peterson. 2000. NOD Idd5 locus controls insulitis and diabetes and overlaps the orthologous CTLA4/IDDM12 and NRAMP1 loci in humans. Diabetes 49: 1744-1747.
16. Wicker, L. S., G. Chamberlain, K. Hunter, D. Rainbow, S. Howlett, P. Tiffen, J. Clark, A. Gonzalez-Munoz, A. M. Cumiskey, R. L. Rosa, et al. 2004. 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. 173: 164-173.
17. Hunter, K., D. Rainbow, V. Plagnol, J. A. Todd, L. B. Peterson, and L. S. Wicker. 2007. Interactions between Idd5.1/Ctla4 and other type 1 diabetes genes. J. Immunol. 179: 8341-8349.
18. Robles, D. T., G. S. Eisenbarth, N. J. Dailey, L. B. Peterson, and L. S. Wicker. 2003. Insulin autoantibodies are associated with islet inflammation but not always related to diabetes progression in NOD congenic mice. Diabetes 52: 882-886.
19. Wicker, L. S., J. A. Todd, J. B. Prins, P. L. Podolin, R. J. Renjilian, and L. B. Peterson. 1994. Resistance alleles at two non-major histocompatibility complex-linked insulin-dependent diabetes loci on chromosome 3, Idd3 and Idd10, protect nonobese diabetic mice from diabetes. J. Exp. Med. 180: 1705-1713.
20. Denny, P., C. J. Lord, N. J. Hill, J. V. Goy, E. R. Levy, P. L. Podolin, L. B. Peterson, L. S. Wicker, J. A. Todd, and P. A. Lyons. 1997. Mapping of the IDDM locus Idd3 to a 0.35-cM interval containing the interleukin-2 gene. Diabetes 46: 695-700.
21. Lyons, P. A., and L. S. Wicker. 1999. Localising quantitative trait loci in the NOD mouse model of type 1 diabetes. Curr. Dir. Autoimmun. 1: 208-225.
22. Lyons, P. A., N. Armitage, F. Argentina, P. Denny, N. J. Hill, C. J. Lord, M. B. Wilusz, L. B. Peterson, L. S. Wicker, and J. A. Todd. 2000. Congenic mapping of the type 1 diabetes locus, Idd3, to a 780-kb region of mouse chromosome 3: identification of a candidate segment of ancestral DNA by haplotype mapping. Genome Res. 10: 446-453.
23. Podolin, P. L., M. B. Wilusz, R. M. Cubbon, U. Pajvani, C. J. Lord, J. A. Todd, L. B. Peterson, L. S. Wicker, and P. A. Lyons. 2000. Differential glycosylation of interleukin 2, the molecular basis for the NOD Idd3 type 1 diabetes gene? Cytokine 12: 477-482.
24. Yamanouchi, J., D. Rainbow, P. Serra, S. Howlett, K. Hunter, V. E. Garner, A. Gonzalez-Munoz, J. Clark, R. Veijola, R. Cubbon, et al. 2007. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat. Genet. 39: 329-337.
25. McGuire, H. M., A. Vogelzang, N. Hill, M. Flodström-Tullberg, J. Sprent, and C. King. 2009. Loss of parity between IL-2 and IL-21 in the NOD Idd3 locus. Proc. Natl. Acad. Sci. USA 106: 19438-19443.
26. Liu, S. M., D. H. Lee, J. M. Sullivan, D. Chung, A. Jäger, B. O. Shum, N. E. Sarvetnick, A. C. Anderson, and V. K. Kuchroo. 2011. Differential IL-21 signaling in APCs leads to disparate Th17 differentiation in diabetes-susceptible NOD and diabetes-resistant NOD.Idd3 mice. J. Clin. Invest. 121: 4303-4310.
27. Todd, J. A., N. M. Walker, J. D. Cooper, D. J. Smyth, K. Downes, V. Plagnol, R. Bailey, S. Nejentsev, S. F. Field, F. Payne, et al; Genetics of Type 1 Diabetes in Finland; Wellcome Trust Case Control Consortium. 2007. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat. Genet. 39: 857-864.
28. Hamilton-Williams, E. E., X. Martinez, J. Clark, S. Howlett, K. M. Hunter, D. B. Rainbow, L. Wen, M. J. Shlomchik, J. D. Katz, G. F. Beilhack, et al. 2009. Expression of diabetes-associated genes by dendritic cells and CD4 T cells drives the loss of tolerance in nonobese diabetic mice. J. Immunol. 183: 1533-1541.
29. Hamilton-Williams, E. E., J. Cheung, D. B. Rainbow, K. M. Hunter, L. S. Wicker, and L. A. Sherman. 2012. Cellular mechanisms of restored β-cell tolerance mediated by protective alleles of Idd3 and Idd5. Diabetes 61: 166-174.
30. Irie, J., B. Reck, Y. Wu, L. S. Wicker, S. Howlett, D. Rainbow, E. Feingold, and W. M. Ridgway. 2008. Genome-wide microarray expression analysis of CD4+ T cells from nonobese diabetic congenic mice identifies Cd55 (Daf1) and Acadl as candidate genes for type 1 diabetes. J. Immunol. 180: 1071-1079.
31. Ueda, H., J. M. Howson, L. Esposito, J. Heward, H. Snook, G. Chamberlain, D. B. Rainbow, K. M. Hunter, A. N. Smith, G. Di Genova, et al. 2003. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423: 506-511.
32. Howson, J. M., D. B. Dunger, S. Nutland, H. Stevens, L. S. Wicker, and J. A. Todd. 2007. A type 1 diabetes subgroup with a female bias is characterised by failure in tolerance to thyroid peroxidase at an early age and a strong association with the cytotoxic T-lymphocyte-associated antigen-4 gene. Diabetologia 50: 741-746.
33. Vijayakrishnan, L., J. M. Slavik, Z. Illés, R. J. Greenwald, D. Rainbow, B. Greve L. B. Peterson, D. A. Hafler, G. J. Freeman, A. H. Sharpe, et al. 2004. An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells. Immunity 20: 563-575.
34. Araki, M., D. Chung, S. Liu, D. B. Rainbow, G. Chamberlain, V. Garner, K. M. Hunter, L. Vijayakrishnan, L. B. Peterson, M. Oukka, et al. 2009. 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. 183: 5146-5157.
35. Runstadler, J. A., H. Säilä, A. Savolainen, M. Leirisalo-Repo, K. Aho, E. Tuomilehto-Wolf, J. Tuomilehto, and M. F. Seldin. 2005. Association of SLC11A1 (NRAMP1) with persistent oligoarticular and polyarticular rheumatoid factor-negative juvenile idiopathic arthritis in Finnish patients: haplotype analysis in Finnish families. Arthritis Rheum. 52: 247-256.
36. Shaw, M. A., D. Clayton, S. E. Atkinson, H. Williams, N. Miller, D. Sibthorpe, and J. M. Blackwell. 1996. Linkage of rheumatoid arthritis to the candidate gene NRAMP1 on 2q35. J. Med. Genet. 33: 672-677.
37. Vidal, S. M., D. Malo, K. Vogan, E. Skamene, and P. Gros. 1993. Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell 73: 469-485.
38. Cellier, M., G. Govoni, S. Vidal, T. Kwan, N. Groulx, J. Liu, F. Sanchez, E. Skamene, E. Schurr, and P. Gros. 1994. Human natural resistance-associated macrophage protein: cDNA cloning, chromosomal mapping, genomic organization, and tissue-specific expression. J. Exp. Med. 180: 1741-1752.
39. Malo, D., K. Vogan, S. Vidal, J. Hu, M. Cellier, E. Schurr, A. Fuks, N. Bumstead, K. Morgan, and P. Gros. 1994. Haplotype mapping and sequence analysis of the mouse Nramp gene predict susceptibility to infection with intracellular parasites. Genomics 23: 51-61.
40. Blackwell, J. M. 1996. Structure and function of the natural- resistanceassociated macrophage protein (Nramp1), a candidate protein for infectious and autoimmune disease susceptibility. Mol. Med. Today 2: 205-211.
41. Gruenheid, S., E. Pinner, M. Desjardins, and P. Gros. 1997. Natural resistance to infection with intracellular pathogens: the Nramp1 protein is recruited to the membrane of the phagosome. J. Exp. Med. 185: 717-730.
42. Searle, S., N. A. Bright, T. I. Roach, P. G. Atkinson, C. H. Barton, R. H. Meloen, and J. M. Blackwell. 1998. Localisation of Nramp1 in macrophages: modulation with activation and infection. J. Cell Sci. 111: 2855-2866.
43. Stober, C. B., S. Brode, J. K. White, J. F. Popoff, and J. M. Blackwell. 2007. Slc11a1, formerly Nramp1, is expressed in dendritic cells and influences major histocompatibility complex class II expression and antigen-presenting cell function. Infect. Immun. 75: 5059-5067.
44. Kissler, S., P. Stern, K. Takahashi, K. Hunter, L. B. Peterson, and L. S. Wicker. 2006. In vivo RNA interference demonstrates a role for Nramp1 in modifying susceptibility to type 1 diabetes. Nat. Genet. 38: 479-483.
45. Dai, Y. D., I. G. Marrero, P. Gros, H. Zaghouani, L. S. Wicker, and E. E. Sercarz. 2009. Slc11a1 enhances the autoimmune diabetogenic T-cell response by altering processing and presentation of pancreatic islet antigens. Diabetes 58: 156-164.
46. Matsubara, Y., Y. Indo, E. Naito, H. Ozasa, R. Glassberg, J. Vockley, Y. Ikeda, J. Kraus, and K. Tanaka. 1989. Molecular cloning and nucleotide sequence of cDNAs encoding the precursors of rat long chain acyl-coenzyme A, short chain acyl-coenzyme A, and isovaleryl-coenzyme A dehydrogenases: sequence homology of four enzymes of the acyl-CoA dehydrogenase family. J. Biol. Chem. 264: 16321-16331.
47. Fox, C. J., P. S. Hammerman, and C. B. Thompson. 2005. Fuel feeds function: energy metabolism and the T-cell response. Nat. Rev. Immunol. 5: 844-852.
48. Deberardinis, R. J., J. J. Lum, and C. B. Thompson. 2006. Phosphatidylinositol 3-kinase-dependent modulation of carnitine palmitoyltransferase 1A expression regulates lipid metabolism during hematopoietic cell growth. J. Biol. Chem. 281: 37372-37380.
49. Pearce, E. L., M. C. Walsh, P. J. Cejas, G. M. Harms, H. Shen, L. S. Wang, R. G. Jones, and Y. Choi. 2009. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 460: 103-107.
50. Cordell, H. J., J. A. Todd, N. J. Hill, C. J. Lord, P. A. Lyons, L. B. Peterson, L. S. Wicker, and D. G. Clayton. 2001. Statistical modeling of interlocus interactions in a complex disease: rejection of the multiplicative model of epistasis in type 1 diabetes. Genetics 158: 357-367.
51. Vidal, S., M. L. Tremblay, G. Govoni, S. Gauthier, G. Sebastiani, D. Malo, E. Skamene, M. Olivier, S. Jothy, and P. Gros. 1995. The Ity/Lsh/Bcg locus: natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene. J. Exp. Med. 182: 655-666.
52. Hulbert, E. M., L. J. Smink, E. C. Adlem, J. E. Allen, D. B. Burdick, O. S. Burren, V. M. Cassen, C. C. Cavnor, G. E. Dolman, D. Flamez, et al. 2007. T1DBase: integration and presentation of complex data for type 1 diabetes research. Nucleic Acids Res. 35(Database issue): D742-D746.
53. Smink, L. J., E. M. Helton, B. C. Healy, C. C. Cavnor, A. C. Lam, D. Flamez, O. S. Burren, Y. Wang, G. E. Dolman, D. B. Burdick, et al. 2005. T1DBase, a community web-based resource for type 1 diabetes research. Nucleic Acids Res. 33(Database issue): D544-D549.
54. Stein, L. D., C. Mungall, S. Shu, M. Caudy, M. Mangone, A. Day, E. Nickerson, J. E. Stajich, T. W. Harris, A. Arva, and S. Lewis. 2002. The generic genome browser: a building block for a model organism system database. Genome Res. 12: 1599-1610.
55. Hamilton-Williams, E. E., S. B. Wong, X. Martinez, D. B. Rainbow, K. M. Hunter, L. S. Wicker, and L. A. Sherman. 2010. Idd9.2 and Idd9.3 protective alleles function in CD4+ T-cells and nonlymphoid cells to prevent expansion of pathogenic islet-specific CD8+ T-cells. Diabetes 59: 1478-1486.
56. Trudeau, J. D., C. Kelly-Smith, C. B. Verchere, J. F. Elliott, J. P. Dutz, D. T. Finegood, P. Santamaria, and R. Tan. 2003. Prediction of spontaneous autoimmune diabetes in NOD mice by quantification of autoreactive T cells in peripheral blood. J. Clin. Invest. 111: 217-223.
57. Martinez, X., H. T. Kreuwel, W. L. Redmond, R. Trenney, K. Hunter, H. Rosen, N. Sarvetnick, L. S. Wicker, and L. A. Sherman. 2005. CD8+ T cell tolerance in nonobese diabetic mice is restored by insulin-dependent diabetes resistance alleles. J. Immunol. 175: 1677-1685.
58. Hamilton-Williams, E. E., X. Martinez, M. Lyman, K. Hunter, L. S. Wicker, and L. A. Sherman. 2007. The use of idd congenic mice to identify checkpoints of peripheral tolerance to islet antigen. Ann. N. Y. Acad. Sci. 1103: 118-127.
59. Jiang, W., M. S. Anderson, R. Bronson, D. Mathis, and C. Benoist. 2005. Modifier loci condition autoimmunity provoked by Aire deficiency. J. Exp. Med. 202: 805-815.
60. Goudy, K. S., M. C. Johnson, A. Garland, C. Li, R. J. Samulski, B. Wang, and R. Tisch. 2011. Reduced IL-2 expression in NOD mice leads to a temporal increase in CD62Llo FoxP3+ CD4+ T cells with limited suppressor activity. Eur. J. Immunol. 41: 1480-1490.
61. Granucci, F., C. Vizzardelli, N. Pavelka, S. Feau, M. Persico, E. Virzi, M. Rescigno, G. Moro, and P. Ricciardi-Castagnoli. 2001. Inducible IL-2 production by dendritic cells revealed by global gene expression analysis. Nat. Immunol. 2: 882-888.
62. Wuest, S. C., J. H. Edwan, J. F. Martin, S. Han, J. S. Perry, C. M. Cartagena, E. Matsuura, D. Maric, T. A. Waldmann, and B. Bielekova. 2011. A role for interleukin-2 trans-presentation in dendritic cell-mediated T cell activation in humans, as revealed by daclizumab therapy. Nat. Med. 17: 604-609.
63. Guerra, C., R. A. Koza, K. Walsh, D. M. Kurtz, P. A. Wood, and L. P. Kozak. 1998. Abnormal nonshivering thermogenesis in mice with inherited defects of fatty acid oxidation. J. Clin. Invest. 102: 1724-1731.
64. Kurtz, D. M., P. Rinaldo, W. J. Rhead, L. Tian, D. S. Millington, J. Vockley, D. A. Hamm, A. E. Brix, J. R. Lindsey, C. A. Pinkert, et al. 1998. Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation. Proc. Natl. Acad. Sci. USA 95: 15592-15597.
65. Cox, K. B., D. A. Hamm, D. S. Millington, D. Matern, J. Vockley, P. Rinaldo, C. A. Pinkert, W. J. Rhead, J. R. Lindsey, and P. A. Wood. 2001. Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse. Hum. Mol. Genet. 10: 2069-2077.
66. Jackson, A. L., and P. S. Linsley. 2004. Noise amidst the silence: off-target effects of siRNAs? Trends Genet. 20: 521-524.
67. Qiu, S., C. M. Adema, and T. Lane. 2005. A computational study of off-target effects of RNA interference. Nucleic Acids Res. 33: 1834-1847.