Gene Symbol: Idd3
Description: insulin dependent diabetes susceptibility 3
Alias: Idd-3, insulin dependent diabetes susceptibility 3
Species: mouse

Top Publications

  1. Koarada S, Wu Y, Fertig N, Sass D, Nalesnik M, Todd J, et al. Genetic control of autoimmunity: protection from diabetes, but spontaneous autoimmune biliary disease in a nonobese diabetic congenic strain. J Immunol. 2004;173:2315-23 pubmed
  2. Matsuki N, Stanic A, Embers M, Van Kaer L, Morel L, Joyce S. Genetic dissection of V alpha 14J alpha 18 natural T cell number and function in autoimmune-prone mice. J Immunol. 2003;170:5429-37 pubmed
    ..The most notable of these map to the Idd4, Idd5, Idd9.1, and Idd13 regions of the mouse genome. Together these findings provide a clue to the genetic mechanism(s) underlying iNKT cell deficiency in NOD mice...
  3. McGuire H, Vogelzang A, Hill N, Flodstrom Tullberg M, Sprent J, King C. Loss of parity between IL-2 and IL-21 in the NOD Idd3 locus. Proc Natl Acad Sci U S A. 2009;106:19438-43 pubmed publisher
    ..the strongest non-MHC-linked locus for type 1 diabetes (T1D) susceptibility on the nonobese diabetic (NOD) mouse (Idd3)...
  4. Lyons P, Armitage N, Argentina F, Denny P, Hill N, Lord C, et al. 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. 2000;10:446-53 pubmed
    ..Previously, we have mapped one of these loci, Idd3, to a 0.35-cM interval on proximal mouse chromosome 3...
  5. Pearson T, Weiser P, Markees T, Serreze D, Wicker L, Peterson L, et al. Islet allograft survival induced by costimulation blockade in NOD mice is controlled by allelic variants of Idd3. Diabetes. 2004;53:1972-8 pubmed
    ..After costimulation blockade, islet allograft survival was prolonged in diabetes-resistant NOD.B6 Idd3 mice and shortened in diabetes-free C57BL/6 mice congenic for the NOD Idd3 variant...
  6. Lin X, Hamilton Williams E, Rainbow D, Hunter K, Dai Y, Cheung J, 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;190:3109-20 pubmed publisher
    ..Independently, protective alleles of Idd3/Il2 or Idd5 are able to partially protect congenic NOD mice from insulitis and diabetes, and to partially tolerize ..
  7. Wicker L, Todd J, Prins J, Podolin P, Renjilian R, Peterson L. 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. 1994;180:1705-13 pubmed the outcross partner, we previously identified several non-MHC Idd loci, including two located on chromosome 3 (Idd3 and Idd10)...
  8. D Alise A, Auyeung V, Feuerer M, Nishio J, Fontenot J, Benoist C, et al. The defect in T-cell regulation in NOD mice is an effect on the T-cell effectors. Proc Natl Acad Sci U S A. 2008;105:19857-62 pubmed publisher
    ..This difference was independent of autoimmune inflammation, did not map to the idd3 region, and was not due to the overproduction of interleukin-21 in NOD mice...
  9. del Rio R, Noubade R, Subramanian M, Saligrama N, Diehl S, Rincon M, et al. SNPs upstream of the minimal promoter control IL-2 expression and are candidates for the autoimmune disease-susceptibility locus Aod2/Idd3/Eae3. Genes Immun. 2008;9:115-21 pubmed publisher
    ..these SNPs segregate with differential production of IL-2 by CD4(+) T cells as well as susceptibility alleles at Idd3 and Eae3, QTL controlling insulin-dependent diabetes mellitus and experimental allergic encephalomyelitis...

More Information


  1. Yamanouchi J, Rainbow D, Serra P, Howlett S, Hunter K, Garner V, et al. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet. 2007;39:329-37 pubmed
    ..Here, we show that autoimmune disease susceptibility and resistance alleles on mouse chromosome 3 (Idd3) correlate with differential expression of the key immunoregulatory cytokine interleukin-2 (IL-2)...
  2. Nguyen C, Kim H, Cornelius J, Peck A. Development of Sjogren's syndrome in nonobese diabetic-derived autoimmune-prone C57BL/6.NOD-Aec1Aec2 mice is dependent on complement component-3. J Immunol. 2007;179:2318-29 pubmed
  3. Zucchelli S, Holler P, Yamagata T, Roy M, Benoist C, Mathis D. Defective central tolerance induction in NOD mice: genomics and genetics. Immunity. 2005;22:385-96 pubmed
    ..Intersection of the data from the two approaches points to a small set of attractive candidate genes. ..
  4. Hill N, Lyons P, Armitage N, Todd J, Wicker L, Peterson L. NOD Idd5 locus controls insulitis and diabetes and overlaps the orthologous CTLA4/IDDM12 and NRAMP1 loci in humans. Diabetes. 2000;49:1744-7 pubmed
    ..provides a significant amount of protection from diabetes (50% reduction from parental frequency) and when combined with another resistance locus (Idd3 on chromosome 3), provides nearly complete protection from diabetes and insulitis.
  5. Podolin P, Denny P, Lord C, Hill N, Todd J, Peterson L, et al. Congenic mapping of the insulin-dependent diabetes (Idd) gene, Idd10, localizes two genes mediating the Idd10 effect and eliminates the candidate Fcgr1. J Immunol. 1997;159:1835-43 pubmed
    ..The Idd3 gene, originally defined as a broad peak of linkage on mouse chromosome 3, was subsequently identified as two genes,..
  6. Hunter K, Rainbow D, Plagnol V, Todd J, Peterson L, Wicker L. Interactions between Idd5.1/Ctla4 and other type 1 diabetes genes. J Immunol. 2007;179:8341-9 pubmed
    ..This masking of CTLA-4 alleles by different genetic backgrounds provides an explanation for our observation that the human CTLA-4 gene is only associated with T1D in the subgroup of human T1D patients with anti-thyroid autoimmunity...
  7. Liu S, Lee D, Sullivan J, Chung D, Jäger A, Shum B, et al. Differential IL-21 signaling in APCs leads to disparate Th17 differentiation in diabetes-susceptible NOD and diabetes-resistant NOD.Idd3 mice. J Clin Invest. 2011;121:4303-10 pubmed publisher
    ..The mouse T1D susceptibility locus insulin-dependent diabetes susceptibility 3 (Idd3), which has a homologous genetic interval in humans, encodes cytokine genes Il2 and Il21 and regulates diabetes and ..
  8. Hamilton Williams E, Cheung J, Rainbow D, Hunter K, Wicker L, Sherman L. Cellular mechanisms of restored β-cell tolerance mediated by protective alleles of Idd3 and Idd5. Diabetes. 2012;61:166-74 pubmed publisher
    ..In NOD mice, when present together, protective alleles encoding IL-2, Idd3 candidate gene, CTLA-4, NRAMP1, and acetyl-coenzyme A dehydrogenase, long-chain (ACADL) (candidate genes for the ..
  9. McDuffie M. Genetics of autoimmune diabetes in animal models. Curr Opin Immunol. 1998;10:704-9 pubmed
    ..In addition, mice carrying transgenes and null mutations related to T cell function have been used to demonstrate potential mechanisms for both MHC-dependence and specific effector functions, such as cytokine release and cytotoxicity. ..
  10. Nguyen C, Singson E, Kim J, Cornelius J, Attia R, Doyle M, et al. Sjögren's syndrome-like disease of C57BL/6.NOD-Aec1 Aec2 mice: gender differences in keratoconjunctivitis sicca defined by a cross-over in the chromosome 3 Aec1 locus. Scand J Immunol. 2006;64:295-307 pubmed
    ..These data suggest SjS-like disease in the NOD mouse shows gender-specific regulation determined by autosomal genes...
  11. Cha S, Nagashima H, Brown V, Peck A, Humphreys Beher M. Two NOD Idd-associated intervals contribute synergistically to the development of autoimmune exocrinopathy (Sjögren's syndrome) on a healthy murine background. Arthritis Rheum. 2002;46:1390-8 pubmed
    ..susceptibility in the NOD mouse model have been identified, but only 2 chromosomal intervals (associated with Idd3 and Idd5) have been shown to control sialadenitis...
  12. Podolin P, Wilusz M, Cubbon R, Pajvani U, Lord C, Todd J, et al. Differential glycosylation of interleukin 2, the molecular basis for the NOD Idd3 type 1 diabetes gene?. Cytokine. 2000;12:477-82 pubmed
    The insulin-dependent diabetes (Idd) gene, Idd3, has been localised to a 0.35 cM region of chromosome 3 containing the structural gene for the cytokine interleukin 2 (IL-2)...
  13. Teuscher C, Wardell B, Lunceford J, Michael S, Tung K. Aod2, the locus controlling development of atrophy in neonatal thymectomy-induced autoimmune ovarian dysgenesis, co-localizes with Il2, Fgfb, and Idd3. J Exp Med. 1996;183:631-7 pubmed
    ..Most significant, however, is the co-localization of Aod2 to Idd3, a susceptibility gene that plays a role in autoimmune insulin-dependent type 1 diabetes mellitus in the nonobese ..
  14. Boulard O, Fluteau G, Eloy L, Damotte D, Bedossa P, Garchon H. Genetic analysis of autoimmune sialadenitis in nonobese diabetic mice: a major susceptibility region on chromosome 1. J Immunol. 2002;168:4192-201 pubmed
    ..1, 2, 3, 9, and 17, corresponding to Idd5, Idd13, Idd3, Idd2, and Idd1, respectively), accounting for the strong linkage previously reported between insulitis and ..
  15. Lundholm M, Motta V, Löfgren Burström A, Duarte N, Bergman M, Mayans S, et al. Defective induction of CTLA-4 in the NOD mouse is controlled by the NOD allele of Idd3/IL-2 and a novel locus (Ctex) telomeric on chromosome 1. Diabetes. 2006;55:538-44 pubmed
    ..Using a genetic approach we here demonstrate that a novel locus (Ctex) telomeric on chromosome 1 together with the Idd3 (Il-2) gene confers optimal CTLA-4 expression upon CD3 activation of T-cells...
  16. Kochupurakkal N, Kruger A, Tripathi S, Zhu B, Adams L, Rainbow D, et al. Blockade of the programmed death-1 (PD1) pathway undermines potent genetic protection from type 1 diabetes. PLoS ONE. 2014;9:e89561 pubmed publisher
    ..type 1 diabetes in nearly all NOD Idd congenic strains tested, despite the fact that all are moderately (Idd5, Idd3 and Idd10/18) or highly (Idd3/10/18 and Idd9) protected from spontaneous type 1 diabetes by virtue of their ..
  17. Ikegami H, Fujisawa T, Makino S, Ogihara T. Congenic mapping and candidate sequencing of susceptibility genes for Type 1 diabetes in the NOD mouse. Ann N Y Acad Sci. 2003;1005:196-204 pubmed
    ..Phenotypes of NOD. IIS-Idd3 congenic mice, which share the same alleles at both Il2 and Il21 as the NOD mouse, were indistinguishable from the ..
  18. Lundholm M, Mayans S, Motta V, Löfgren Burström A, Danska J, Holmberg D. Variation in the Cd3 zeta (Cd247) gene correlates with altered T cell activation and is associated with autoimmune diabetes. J Immunol. 2010;184:5537-44 pubmed publisher
    ..These results support a model in which the development of autoimmune diabetes is dependent on a TCR signal mediated by a less-efficient NOD allele of the Cd3zeta gene. ..
  19. Cornall R. Genetics of a multifactorial disease: autoimmune type 1 diabetes mellitus. Clin Sci (Lond). 1993;84:257-62 pubmed
    ..3. The homologues of these genes may reside on human chromosomes 1 or 4 (Idd-3), 17 (Idd-4) and 2q (Idd-5). ..
  20. Brayer J, Lowry J, Cha S, Robinson C, Yamachika S, Peck A, et al. Alleles from chromosomes 1 and 3 of NOD mice combine to influence Sjögren's syndrome-like autoimmune exocrinopathy. J Rheumatol. 2000;27:1896-904 pubmed
    ..Replacement of individual diabetes susceptibility intervals Idd3, Idd5, Idd13, Idd1, and Idd9, as well as a combination of the Idd3, Idd10, and Idd17 intervals, with resistance ..
  21. Lord C, Bohlander S, Hopes E, Montague C, Hill N, Prins J, et al. Mapping the diabetes polygene Idd3 on mouse chromosome 3 by use of novel congenic strains. Mamm Genome. 1995;6:563-70 pubmed
    Development of novel congenic mouse strains has allowed us to better define the location of the diabetogenic locus, Idd3, on Chromosome (Chr) 3...
  22. Todd J, Aitman T, Cornall R, Ghosh S, Hall J, Hearne C, et al. Genetic analysis of autoimmune type 1 diabetes mellitus in mice. Nature. 1991;351:542-7 pubmed
    ..On the basis of comparative maps of the mouse and human genomes, the homologue of Idd-3 may reside on human chromosomes 1 or 4 and Idd-4 on chromosome 17. ..
  23. Prochazka M, Leiter E, Serreze D, Coleman D. Three recessive loci required for insulin-dependent diabetes in nonobese diabetic mice. Science. 1987;237:286-9 pubmed
  24. Encinas J, Wicker L, Peterson L, Mukasa A, Teuscher C, Sobel R, et al. QTL influencing autoimmune diabetes and encephalomyelitis map to a 0.15-cM region containing Il2. Nat Genet. 1999;21:158-60 pubmed
  25. Nguyen C, Sharma A, She J, McIndoe R, Peck A. Differential gene expressions in the lacrimal gland during development and onset of keratoconjunctivitis sicca in Sjögren's syndrome (SJS)-like disease of the C57BL/6.NOD-Aec1Aec2 mouse. Exp Eye Res. 2009;88:398-409 pubmed publisher
  26. Nguyen C, Yin H, Lee B, Chiorini J, Peck A. IL17: potential therapeutic target in Sjögren's syndrome using adenovirus-mediated gene transfer. Lab Invest. 2011;91:54-62 pubmed publisher
    ..Thus, therapeutic approach targeting IL17 may be effective in preventing glandular dysfunction. ..
  27. Sgouroudis E, Albanese A, Piccirillo C. Impact of protective IL-2 allelic variants on CD4+ Foxp3+ regulatory T cell function in situ and resistance to autoimmune diabetes in NOD mice. J Immunol. 2008;181:6283-92 pubmed
    Type I diabetes (T1D) susceptibility is inherited through multiple insulin-dependent diabetes (Idd) genes. NOD.B6 Idd3 congenic mice, introgressed with an Idd3 allele from T1D-resistant C57BL/6 mice (Idd3(B6)), show a marked resistance to ..
  28. Cha S, Nagashima H, Peck A, Humphreys Beher M. IDD3 and IDD5 alleles from nod mice mediate Sjögren's syndrome-like autoimmunity. Adv Exp Med Biol. 2002;506:1035-9 pubmed
  29. Denny P, Lord C, Hill N, Goy J, Levy E, Podolin P, et al. Mapping of the IDDM locus Idd3 to a 0.35-cM interval containing the interleukin-2 gene. Diabetes. 1997;46:695-700 pubmed
    ..To fine map these loci, we used congenic mapping. Using this approach, we localized the Idd3 locus to a 0.35-cM interval on chromosome 3 containing the Il2 gene...
  30. Su X, Hu Q, Kristan J, Costa C, Shen Y, Gero D, et al. Significant role for Fas in the pathogenesis of autoimmune diabetes. J Immunol. 2000;164:2523-32 pubmed
    ..These results provide evidence that Fas/FasL-mediated programmed cell death plays a significant role in the pathogenesis of autoimmune diabetes. ..
  31. Wilson E, Livingstone A. Cutting edge: CD4+ T cell-derived IL-2 is essential for help-dependent primary CD8+ T cell responses. J Immunol. 2008;181:7445-8 pubmed
    ..We suggest that it is also a critical component of help for CD8(+) T cell responses to pathogens, because protective memory also requires CD8(+) T cell stimulation by IL-2 during priming. ..
  32. Prins J, Todd J, Rodrigues N, Ghosh S, Hogarth P, Wicker L, et al. Linkage on chromosome 3 of autoimmune diabetes and defective Fc receptor for IgG in NOD mice. Science. 1993;260:695-8 pubmed
    ..The development of congenic strains and the characterization of Mendelian traits that are specific to the disease phenotype demonstrate the feasibility of dissecting the pathophysiology of complex, non-Mendelian diseases. ..
  33. Ikegami H, Fujisawa T, Makino S, Ogihara T. Genetic dissection of type 1 diabetes susceptibility gene, Idd3, by ancestral haplotype congenic mapping. Ann N Y Acad Sci. 2002;958:325-8 pubmed
    One of the strongest non-MHC susceptibility genes for type 1 diabetes, Idd3, has been mapped to a 0.15-cM segment of chromosome 3, where a strong candidate gene, Il2, encoding cytokine IL2, is located...
  34. Jiang W, Anderson M, Bronson R, Mathis D, Benoist C. Modifier loci condition autoimmunity provoked by Aire deficiency. J Exp Med. 2005;202:805-15 pubmed
  35. Mangada J, Pearson T, Brehm M, Wicker L, Peterson L, Shultz L, et al. Idd loci synergize to prolong islet allograft survival induced by costimulation blockade in NOD mice. Diabetes. 2009;58:165-73 pubmed publisher
    ..The frequency of diabetes is reduced in NOD.B6 Idd3 mice and is virtually absent in NOD.B6/B10 Idd3 Idd5 mice. Islet allograft survival in NOD...
  36. Yui M, Muralidharan K, Moreno Altamirano B, Perrin G, Chestnut K, Wakeland E. Production of congenic mouse strains carrying NOD-derived diabetogenic genetic intervals: an approach for the genetic dissection of complex traits. Mamm Genome. 1996;7:331-4 pubmed
    ..These results demonstrate the utility of this congenic approach for the study of complex genetic traits. ..
  37. Haddad R, Morrow A, Plass C, Held W. Restriction landmark genomic scanning of mouse liver tumors for gene amplification: overexpression of cyclin A2. Biochem Biophys Res Commun. 2000;274:188-96 pubmed
    ..Our results also indicate that our mouse model for liver tumorigenesis in mice accurately recapitulates events observed in human hepatocellular carcinoma. ..
  38. Moritoki Y, Tsuda M, Tsuneyama K, Zhang W, Yoshida K, Lian Z, et al. B cells promote hepatic inflammation, biliary cyst formation, and salivary gland inflammation in the NOD.c3c4 model of autoimmune cholangitis. Cell Immunol. 2011;268:16-23 pubmed publisher
    ..c3c4 mice, illustrating a critical role of B cells in modulating specific organ pathology and, in particular, in exacerbating both the biliary disease and the sialadenitis. ..
  39. Ghosh S, Palmer S, Rodrigues N, Cordell H, Hearne C, Cornall R, et al. Polygenic control of autoimmune diabetes in nonobese diabetic mice. Nat Genet. 1993;4:404-9 pubmed
  40. Kornete M, Sgouroudis E, Piccirillo C. ICOS-dependent homeostasis and function of Foxp3+ regulatory T cells in islets of nonobese diabetic mice. J Immunol. 2012;188:1064-74 pubmed publisher
    ..Overall, ICOS is critical for the homeostasis and functional stability of Foxp3(+) Tregs in prediabetic islets and maintenance of T1D protection...
  41. McAleer M, Reifsnyder P, Palmer S, Prochazka M, Love J, Copeman J, et al. Crosses of NOD mice with the related NON strain. A polygenic model for IDDM. Diabetes. 1995;44:1186-95 pubmed
    ..Diabetogenic NOD-derived alleles at Idd2 (Chr 9), Idd3 (Chr 3), and Idd10 (Chr 3) were segregating in the BC1...