Skip to main content
Log in

The Non Obese Diabetic (NOD) Mouse: A Unique Model for Understanding the Interaction Between Genetics and T Cell Responses

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Wicker LS, Miller BJ, Mullen Y. Transfer of autoimmune diabetes mellitus with splenocytes from nonobese diabetic (NOD) mice. Diabetes 1986;35:855.

    Google Scholar 

  2. Haskins K, McDuffie M. Acceleration of diabetes in young NOD mice with a CD4+ islet-specific T cell clone. Science 1990;249:1433.

    Google Scholar 

  3. Christianson SW, Shultz LD, Leiter EH. Adoptive transfer of diabetes into immunodeficient NOD-scid/scid mice. Relative contributions of CD4+ and CD8+ T-cells from diabetic versus prediabetic NOD. NON-Thy-1a donors. Diabetes 1993;42:44.

    Google Scholar 

  4. Lejon K, Fathman CG. Isolation of self antigen-reactive cells from inflamed islets of nonobese diabetic mice using CD4high expression as a marker. J Immunol 1999;163:5708.

    Google Scholar 

  5. Shizuru JA, Taylor-Edwards C, Banks BA, Gregory AK, Fathman CG. Immunotherapy of the nonobese diabetic mouse: Treatment with an antibody to T-helper lymphocytes. Science 1988;240:659.

    Google Scholar 

  6. Chatenoud L, Thervet E, Primo J, Bach JF. Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc Natl Acad Sci USA 1994;91:123.

    Google Scholar 

  7. Acha-Orbea H, McDevitt HO. The first external domain of the nonobese diabetic mouse class II I-A beta chain is unique. Proc Natl Acad Sci USA 1987;84:2435.

    Google Scholar 

  8. Wicker LS, Miller BJ, Coker LZ, McNally SE, Scott S, Mullen Y, Appel MC. Genetic control of diabetes and insulitis in the nonobese diabetic (NOD) mouse. J Exp Med 1987;165:1639.

    Google Scholar 

  9. Mosmann TR, Coffman RL. TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989;7:145.

    Google Scholar 

  10. O'Garra A, Steinman L, Gijbels K. CD4+ T-cell subsets in autoimmunity. Curr Opin Immunol 1997;9:872.

    Google Scholar 

  11. Rabinovitch A. Immunoregulatory and cytokine imbalances in the pathogenesis of IDDM. Therapeutic intervention by immunostimulation? (see comments). Diabetes 1994;43:613.

    Google Scholar 

  12. Adorini L, Trembleau S. Immune deviation towards Th2 inhibits Th-1-mediated autoimmune diabetes. Biochem Soc Trans 1997;25: 625.

    Google Scholar 

  13. Katz JD, Benoist C, Mathis D. T helper cell subsets in insulindependent diabetes. Science 1995;268:1185.

    Google Scholar 

  14. Liblau RS, Singer SM, McDevitt HO. Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases (see comments). Immunol Today 1995;16:34.

    Google Scholar 

  15. Fox CJ, Danska JS. IL-4 expression at the onset of islet inflammation predicts nondestructive insulitis in nonobese diabetic mice. J Immunol 1997;158:2414.

    Google Scholar 

  16. Rabinovitch A. An update on cytokines in the pathogenesis of insulin-dependent diabetes mellitus. Diabetes Metab Rev 1998;14:129.

    Google Scholar 

  17. Fox CJ, Paterson AD, Mortin-Toth SM, Danska JS. Two genetic loci regulate T cell-dependent islet inflammation and drive autoimmune diabetes pathogenesis. Am J Hum Genet 2000;67:67.

    Google Scholar 

  18. Koarada S, Wu Y, Ridgway WM. Increased entry into the IFN gamma effector pathway by CD4+ T cells selected by I-Ag7 on a nonobese diabetic versus C57BL/6 genetic background. J Immunol 2001;167:1693.

    Google Scholar 

  19. Koarada S, Wu Y, Olshansky G, Ridgway W. Increased nonobese diabetic Th1:Th2 (IFN-γ:IL-4) ratio is CD4+T cell intrinsic and independent of APC genetic background. J Immunol 2002;169:6580–6587.

    Google Scholar 

  20. McDevitt H, Singer S, Tisch R. The role of MHC class II genes in susceptibility and resistance to type I diabetes mellitus in the NOD mouse. Horm Meta Res 1996;28:287.

    Google Scholar 

  21. Ridgway WM, Fathman CG. MHC structure and autoimmune T cell repertoire development. Curr Opin Immunol 1999;11:638.

    Google Scholar 

  22. Ridgway WM, Fasso M, Fathman CG. A new look at MHC and autoimmune disease. Science 1999;284:749.

    Google Scholar 

  23. Zamvil SS, Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol 1990;8:579–621.

    Google Scholar 

  24. Goverman J, Woods A, Larson L, Weiner LP, Hood L, Zaller DM. Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell 1993;72(4):551– 560.

    Google Scholar 

  25. Kuchroo VK, Anderson AC, Waldner H, Munder M, Bettelli E, Nicholson LB. T cell response in experimental autoimmune encephalomyelitis (EAE): Role of self and cross-reactive antigens in shaping, tuning, and regulating the autopathogenic T cell repertoire. Annu Rev Immunol 2002;20:101–123.

    Google Scholar 

  26. Tisch R, Yang XD, Singer SM, Liblau RS, Fugger L, McDevitt HO. Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice (see comments). Nature 1993;366:72.

    Google Scholar 

  27. Kaufman DL, Clare-Salzler M, Tian J, Forsthuber T, Ting GS, Robinson P, Atkinson MA, Sercarz EE, Tobin AJ, Lehmann PV. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes (see comments). Nature 1993;366:69.

    Google Scholar 

  28. Wegmann DR, Gill RG, Norbury-Glaser M, Schloot N, Daniel D. Analysis of the spontaneous T cell response to insulin in NOD mice. J Autoimmun 1994;7:833.

    Google Scholar 

  29. Karges W, Hammond-McKibben D, Gaedigk R, Shibuya N, Cheung R, Dosch HM. Loss of self-tolerance to ICA69 in nonobese diabetic mice. Diabetes 1997;46:1548.

    Google Scholar 

  30. Elias D, Markovits D, Reshef T, van der Zee R, Cohen IR. Induction and therapy of autoimmune diabetes in the non-obese diabetic (NOD/Lt) mouse by a 65-kDa heat shock protein. Proc Natl Acad Sci USA 1990;87:1576.

    Google Scholar 

  31. Katz JD, Wang B, Haskins K, Benoist C, Mathis D. Following a diabetogenic T cell from genesis through pathogenesis. Cell 1993;74:1089.

    Google Scholar 

  32. Tisch R, Yang XD, Liblau RS, McDevitt HO. Administering glutamic acid decarboxylase to NOD mice prevents diabetes. J Autoimmun 1994;7:845.

    Google Scholar 

  33. Petersen JS, Karlsen AE, Markholst H, Worsaae A, Dyrberg T, Michelsen B. Neonatal tolerization with glutamic acid decarboxylase but not with bovine serum albumin delays the onset of diabetes in NOD mice. Diabetes 1994;43:1478.

    Google Scholar 

  34. Elliott JF, Qin HY, Bhatti S, Smith DK, Singh RK, Dillon T, Lauzon J, Singh B. Immunization with the larger isoform of mouse glutamic acid decarboxylase (GAD67) prevents autoimmune diabetes in NOD mice. Diabetes 1994;43:1494.

    Google Scholar 

  35. Tian J, Atkinson MA, Clare-Salzler M, Herschenfeld A, Forsthuber T, Lehmann PV, Kaufman DL. Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes. J Exp Med 1996;183: 1561.

    Google Scholar 

  36. Schloot NC, Daniel D, Norbury-Glaser M, Wegmann DR. Peripheral T cell clones from NOD mice specific for GAD65 peptides: Lack of islet responsiveness or diabetogenicity. J Autoimmun 1996;9: 357.

    Google Scholar 

  37. Plesner A, Worsaae A, Dyrberg T, Gotfredsen C, Michelsen BK, Petersen JS. Immunization of diabetes-prone or non-diabetes-prone mice with GAD65 does not induce diabetes or islet cell pathology. J Autoimmun 1998;11:335.

    Google Scholar 

  38. Kash SF, Condie BG, Baekkeskov S. Glutamate decarboxylase and GABA in pancreatic islets: Lessons from knock-out mice. Horm Metab Res 1999;31:340.

    Google Scholar 

  39. Yang Y, Charlton B, Shimada A, Dal Canto R, Fathman CG. Monoclonal T cells identified in early NOD islet infiltrates. Immunity 1996;4:189.

    Google Scholar 

  40. Shizuru JA, Taylor-Edwards C, Livingstone A, Fathman CG. Genetic dissection of T Cell receptor V beta gene requirements for spontaneous murine diabetes. J Exp Med 1991;174(3):633–638.

    Google Scholar 

  41. Ridgway WM, Fasso M, Lanctot A, Garvey C, Fathman CG. Breaking self-tolerance in nonobese diabetic mice. J Exp Med 1996;183:1657.

    Google Scholar 

  42. Kanagawa O, Martin SM, Vaupel BA, Carrasco-Marin E, Unanue ER. Autoreactivity of T cells from nonobese diabetic mice: An I-Ag7-dependent reaction. Proc Natl Acad Sci USA 1998;95:1721.

    Google Scholar 

  43. Humphreys-Beher MG, Hu Y, Nakagawa Y, Wang PL, Purushotham KR. Utilization of the non-obese diabetic (NOD) mouse as an animal model for the study of secondary Sjogren's syndrome. Adv Exp Med Biol 1994;350:631.

    Google Scholar 

  44. Todd JA, Aitman TJ, Cornall RJ, Ghosh S, Hall JR, Hearne CM, Knight AM, Love JM, McAleer MA, Prins JB, Rodriques W, Lathrop M, Pressey A, Delarto N, Peterson LB, Wicker LS. Genetic analysis of autoimmune type 1 diabetes mellitus in mice (see comments). Nature 1991;351:542.

    Google Scholar 

  45. Prochazka M, Leiter EH, Serreze DV, Coleman DL. Three recessive loci required for insulin-dependent diabetes in nonobese diabetic mice (published erratum appears in Science 1988 Nov 11;242(4880):945). Science 1987;237:286.

    Google Scholar 

  46. Wicker LS, Todd JA, Peterson LB. Genetic control of autoimmune diabetes in the NOD mouse. Annu Rev Immunol 1995;13:179.

    Google Scholar 

  47. Lyons PA, Armitage N, Argentina F, Denny P, Hill NJ, Lord CJ, Wilusz MB, Peterson LB, Wicker LS, Todd JA. 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 (In Process Citation). Genome Res 2000;10:446.

    Google Scholar 

  48. Hill NJ, Lyons PA, Armitage N, Todd JA, Wicker LS, Peterson LB. NOD Idd5 locus controls insulitis and diabetes and overlaps the orthologous CTLA4/IDDM12 and NRAMP1 loci in humans. Diabetes 2000;49:1744.

    Google Scholar 

  49. Mohan C, Morel L, Yang P, Wakeland EK. Genetic dissection of systemic lupus erythematosus pathogenesis: Sle2 on murine chromosome 4 leads to B cell hyperactivity. J Immunol 1997;159:454.

    Google Scholar 

  50. Mohan C, Alas E, Morel L, Yang P, Wakeland EK. Genetic dissection of SLE pathogenesis. Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A/H2B/DNA subnucleosomes. J Clin Invest 1998;101:1362.

    Google Scholar 

  51. Mohan C, Yu Y, Morel L, Yang P, Wakeland EK. Genetic dissection of Sle pathogenesis: Sle3 on murine chromosome 7 impacts T cell activation, differentiation, and cell death. J Immunol 1999;162:6492.

    Google Scholar 

  52. Swain SL. Regulation of the development of helper T cell subsets. Immunol Res 1991;10(3/4):177–182.

    Google Scholar 

  53. Kim JI, Ho IC, Grusby MJ, Glimcher LH. The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines. Immunity 1999;10:745.

    Google Scholar 

  54. Kaplan MH, Schindler U, Smiley ST, Grusby MJ. Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity 1996;4:313.

    Google Scholar 

  55. Zhang DH, Yang L, Cohn L, Parkyn L, Homer R, Ray P, Ray A. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity 1999;11:473.

    Google Scholar 

  56. Kuchroo VK, Das MP, Brown JA, Ranger AM, Zamvil SS, Sobel RA, Weiner HL, Nabavi N, Glimcher LH. B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: Application to autoimmune disease therapy. Cell 1995;80(5):707–718.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ridgway, W.M. The Non Obese Diabetic (NOD) Mouse: A Unique Model for Understanding the Interaction Between Genetics and T Cell Responses. Rev Endocr Metab Disord 4, 263–269 (2003). https://doi.org/10.1023/A:1025104429334

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1025104429334

Navigation