Advertisement

Molecular genetics of insulin-dependent diabetes mellitus: Analysis of congenic strains

  • Hiroshi Ikegami
  • Susumu Makino
  • Toshio Ogihara
Part of the Rev.Ser.Advs.Research Diab.Animals (Birkhäuser) book series (RSARDA, volume 6)

Abstract

Insulin-dependent diabetes mellitus (IDDM) is caused by autoimmune destruction of insulin-producing B-cells of the pancreas in genetically susceptible individuals. Both in animal models and humans, major genetic susceptibility to IDDM has been mapped to the major histocompatibility complex (MHC). In addition, recent genome screening has mapped non-MHC susceptibility genes to chromosomal segments in the mouse and human genomes. For most loci, however, only chromosomal locations are known, with no information on the responsible genes and their functions.

Key words

insulin-dependent diabetes mellitus IDDM genetics NOD mouse congenic mice major histocompatibility complex MHC autoimmune disease ancestral haplotype 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hattori M, Buse JB, Jackson RA, et al. The NOD mouse: Recessive diabetogenic gene in the major histocompatibility complex. Science 231:733–5, 1986.PubMedCrossRefGoogle Scholar
  2. 2.
    Ikegami H, Yano N, Sato T, et al. In: Immunotherapy of diabetes and selected autoimmune diseases. Eisenbarth GS, ed. CRC Press, Boca Raton, FL, pp. 23–33, 1989.Google Scholar
  3. 3.
    Ikegami H, Makino S. In: Lessons from Animal Diabetes IV. Shafrir E, ed. Smith-Gordon, London, 4:39–50, 1993.Google Scholar
  4. 4.
    Acha-Orbea H, McDevitt H. The first external domain of the non-obese diabetic mouse class II I-Aβ chain is unique. Proc Natl Acad Sci USA 84:2435–39, 1987.PubMedCrossRefGoogle Scholar
  5. 5.
    Ikegami H, Makino S, Harada M, et al. The cataract Shionogi mouse, a sister strain of the non-obese diabetic mouse: Similar class II but different class I gene products. Diabetologia 31:254–8, 1988.PubMedCrossRefGoogle Scholar
  6. 6.
    Ikegami H, Eisenbarth G, Hattori M. Major histocompatibility complex-linked diabetogenic gene of the nonobese diabetic mouse: Analysis of genomic DNA amplified by the polymerase chain reaction. J Clin Invest 85:18–24, 1990.PubMedCrossRefGoogle Scholar
  7. 7.
    Koide Y, Yoshida T. The unique nucleotide sequence of the Ab in the NOD mouse is shared with its nondiabetic sister strains, the IL1 and the CTS mouse. Int Immunol 2:189–92, 1989.Google Scholar
  8. 8.
    Liu GY, Baker D, Fairchild S, et al. Complete characterization of the expressed immune response genes in Biozzi AB/H mice: Structural and functional identity between AB/H and NOD A region molecules. Immunogenetics 37:296–300, 1993.PubMedCrossRefGoogle Scholar
  9. 9.
    Wicker LS, Miller BJ, Cocker LZ, et al. Genetic control of diabetes and insulitis in the nonobese diabetic (NOD) mouse. J Exp Med 165:1639–54, 1987.PubMedCrossRefGoogle Scholar
  10. 10.
    Prochazka M, Leiter E, Serreze D, et al. Three recessive loci required for insulin-dependent diabetes in nonobese diabetic mice. Science 237:286–9, 1987.PubMedCrossRefGoogle Scholar
  11. 11.
    Livingstone A, Edwards CT, Shizuru JA, et al. Genetic analysis of diabetes in the nonobese diabetic mouse. I. MHC and T cell receptor beta gene expression. J Immunol 146:529–34, 1991.PubMedGoogle Scholar
  12. 12.
    de Gouyon B, Melanitou E, Richard M, et al. Genetic analysis of diabetes and insulitis in an interspecific cross of the nonobese diabetic mouse with Mus spretus. Proc Natl Acad Sci USA 90:1877–81, 1993.PubMedCrossRefGoogle Scholar
  13. 13.
    Serreze DV, Prochazka M, Reifsnyder PC, et al. Use of recombinant congenic and congenic strains of NOD mice to identify a new insulin-dependent diabetes resistance gene. J Exp Med 180:1553–58, 1994.PubMedCrossRefGoogle Scholar
  14. 14.
    Ghosh S, Palmer S, Rodrigues N, et al. Polygenic control of autoimmune diabetes in nonobese diabetic mice. Nature Genet 4:404–9, 1993.PubMedCrossRefGoogle Scholar
  15. 15.
    Morahan G, McClive P, Huang D, et al. Genetic and physiological association of diabetes susceptibility with raised Na+/H+ exchange activity. Proc Natl Acad Sci USA 91:5898–902, 1994.PubMedCrossRefGoogle Scholar
  16. 16.
    McAleer MA, Reifsnyder P, Palmer SM, et al. Cross of NOD mice with the related NON strain: A polygenic model for IDDM. Diabetes 44:1186–95, 1995.PubMedCrossRefGoogle Scholar
  17. 17.
    Wicker L, Todd J, Peterson L. Genetic control of autoimmune diabetes in the NOD mouse. Annu Rev Immunol 13:179–200, 1995.PubMedCrossRefGoogle Scholar
  18. 18.
    Ikegami H, Makino S, Yamato E, et al. Identification of a new susceptibility locus for insulin-dependent diabetes mellitus by ancestral haplotype congenic mapping. J Clin Invest 96:1936–1942, 1995.PubMedCrossRefGoogle Scholar
  19. 19.
    Makino S, Kunimoto K, Muraoka Y, et al. Breeding of a non-obese, diabetic strain of mice. Exp Anim 29:1–13, 1980.Google Scholar
  20. 20.
    Ikegami H, Kawaguchi Y, Ueda H, et al. MHC-linked diabetogenic gene of the NOD mouse: Molecular mapping of the 3’ boundary of the diabetogenic region. Biochem Biophys Res Commun 192:677–82, 1993.PubMedCrossRefGoogle Scholar
  21. 21.
    Prochazka M, Serreze D, Worthen S, et al. Genetic control of diabetogenesis in NOD/Lt mice: Development and analysis of congenic stocks. Diabetes 38:1446–55, 1989.PubMedCrossRefGoogle Scholar
  22. 22.
    Wicker L, Appel M, Dotta F, et al. Autoimmune syndromes in major histocompatibility complex (MHC) congenic strains of nonobese diabetic (NOD) mice. The NOD MHC is dominant for insulitis and cyclophosphamide-induced diabetes. J Exp Med 176:67–77, 1992.PubMedCrossRefGoogle Scholar
  23. 23.
    Podolin P, Pressey A, DeLarato N, et al. I-E+ nonobese diabetic mice develop insulitis and diabetes. J Exp Med 178:793–803, 1993.PubMedCrossRefGoogle Scholar
  24. 24.
    Ikegami H, Makino S, Hattori M. In: Frontiers of mucosal immunology. Tsuchiya M, ed. 2:429–432, 1991.Google Scholar
  25. 25.
    Miyazaki T, Uno M, Uehira M, et al. Direct evidence for the contribution of the unique I-ANOD to the development of insulitis in non-obese diabetic mouse. Nature 345:722–4, 1990.PubMedCrossRefGoogle Scholar
  26. 26.
    Lund T, O’Reilly L, Hutchings P, et al. Prevention of insulin-dependent diabetes mellitus in non-obese diabetic mice by transgenes encoding modified I-Ab chain or normal I-Ea chain. Nature 345:727–9, 1990.PubMedCrossRefGoogle Scholar
  27. 27.
    Slattery R, Kjer-Nielsen L, Allison J, et al. Prevention of diabetes in non-obese diabetic I-Ak transgenic mice. Nature 345:724–6, 1990.PubMedCrossRefGoogle Scholar
  28. 28.
    Yamato E, Itoh N, Matsumoto E, et al. Second MHC-linked diabetogenic gene located in the proximal side to Lmp-2 in the MHC class I-K region in NOD mice. Diabetes 44(Suppl 1):18A, 1995.Google Scholar
  29. 29.
    Shirai T, Shimizu N, Shiojiri S, et al. Cloning and expression in Escherichia coli of the gene for mouse tumor necrosis factor. DNA 7:193–201, 1988.PubMedCrossRefGoogle Scholar
  30. 30.
    Madema J, Streilein J, Graser R, et al. Nucleotide sequence of the tumor necrosis factor: A gene in seven different inbred strains. Immunogenetics 40:243–4, 1994.CrossRefGoogle Scholar
  31. 31.
    Han J, Huez G, Beutler B. Interactive effects of the tumor necrosis factor promotor and 3’-untranslated regions. J Immunol 146:1843–48, 1991.PubMedGoogle Scholar
  32. 32.
    Pociot F, Briant L, Jongeneel CV, et al. Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-α and TNF-β by human mononuclear cells: A possible link to insulin-dependent diabetes mellitus. Eur J Immunol 23:224–31, 1993.PubMedCrossRefGoogle Scholar
  33. 33.
    Miyazaki T, Matsuda Y, Toyonaga T, et al. Prevention of autoimmune insulitis in nonobese diabetic mice by expression of major histocompatibility complex class I Ld molecules. Proc Natl Acad Sci USA 89:9519–23, 1992.PubMedCrossRefGoogle Scholar
  34. 34.
    Klein J. Biology of the mouse major histocompatibility complex. Springer-Verlag, Berlin, pp. 192–230, 1975.Google Scholar
  35. 35.
    Todd J, Aitman T, Cornall R, et al. Genetic analysis of autoimmune type 1 diabetes mellitus in mice. Nature 351:542–7, 1991.PubMedCrossRefGoogle Scholar
  36. 36.
    Wicker L, Todd J, Prins J-B, et al. Resistance alleles at two non-major histocompatibility complex-linked insulin-dependent diabetes loci on chromosome 3, Idd3 and Iddl0, protect nonobese diabetic mice from diabetes. J Exp Med 180:1705–13, 1994PubMedCrossRefGoogle Scholar
  37. 37.
    Lord C, Bohlander S, Hopes E, et al. Mapping of the diabetes polygene Idd3 on mouse chromosome 3 using novel congenic strains. Mamm Genome 6:563–570, 1995PubMedCrossRefGoogle Scholar
  38. 38.
    Chesnut K, She J-X, Cheng I, et al. Characterization of candidate genes for IDD susceptibility from the diabetes-prone NOD mouse strain. Mamm Genome 4:549–54, 1993PubMedCrossRefGoogle Scholar
  39. 39.
    Prins J-B, Todd J, Rodrigues N, et al. Linkage on chromosome 3 of autoimmune diabetes and defective Fc receptor for IgG in NOD mice. Science 260:695–8, 1993.PubMedCrossRefGoogle Scholar
  40. 40.
    Todd J, Bell J, McDevitt H. HLA-DQβ gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 329:599–604, 1987.PubMedCrossRefGoogle Scholar
  41. 41.
    Todd J, Mijovic C, Fletcher J, et al. Identification of susceptibility loci for insulin-dependent diabetes mellitus by trans-racial gene mapping. Nature 338:587–9, 1989.PubMedCrossRefGoogle Scholar
  42. 42.
    Ikegami H, Kawaguchi Y, Yamato E, et al. Analysis by the polymerase chain reaction of histocompatibility leucocyte antigen-DR9-linked susceptibility to insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 75:1381–85, 1992.PubMedCrossRefGoogle Scholar
  43. 43.
    Hyer RN, Julier C, Buckley JD, et al. High-resolution linkage mapping for susceptibility genes in human polygenic disease: Insulin-dependent diabetes mellitus and chromosome 11q. Am J Hum Genet 48:243–57, 1991.PubMedGoogle Scholar
  44. 44.
    Pritchard LE, Kawaguchi Y, Reed PW, et al. Analysis of the CD3 gene region and type l diabetes: Application of fluorescence-based technology to linkage disequilibrium mapping. Hum Mol Genet 4:197–202, 1995.PubMedCrossRefGoogle Scholar
  45. 45.
    Davies J, Kawaguchi Y, Bennett S, et al. A genome-wide search for human type 1 diabetes susceptibility genes. Nature 371:130–6, 1994.PubMedCrossRefGoogle Scholar
  46. 46.
    Hashimoto L, Habita C, Beressi J, et al. Genetic mapping of a susceptibility locus for insulin-dependent diabetes mellitus on chromosome 11q. Nature 371:161–4, 1994PubMedCrossRefGoogle Scholar
  47. 47.
    Field L, Tobias R, Magnus T. A locus on chromosome 15q26 (IDDM3) produces susceptibility to insulin-dependent diabetes mellitus. Nature Gneet 8:189–94, 1994.CrossRefGoogle Scholar
  48. 48.
    Copeman J, Cucca F, Hearne C, et al. Linkage disequilibrium mapping of a type 1 diabetes susceptibility gene (IDDM7) to chromosome 2q31-q33. Nature Genet 9:80–5, 1995.PubMedCrossRefGoogle Scholar
  49. 49.
    Todd J A. Genetic analysis of type 1 diabetes using whole genome approaches. Proc Natl Acad Sci USA 92:8560–8565, 1995.PubMedCrossRefGoogle Scholar
  50. 50.
    Owerbach D, Gabbay KH. The HOXD8 locus (2q31) is linked to Type I diabetes: Interaction with chromosome 6 and 11 disease susceptibility genes. Diabetes 44:132–6, 1995.PubMedCrossRefGoogle Scholar
  51. 51.
    Luo, Bui MM, Muir A et al. Affected-sibpair mapping of a novel susceptibility gene for insulin-dependent diabetes mellitus (IDDM8) on chromosome 6q25–27. Am J Hum Genet 57:911–9, 1995.PubMedGoogle Scholar
  52. 52.
    Cornall R, Prins J-B, Todd J, et al. Type 1 diabetes in mice is linked to the interleukin-1 receptor and Lsh/Ity/Bcg genes on chromosome 1. Nature 353:262–5, 1991.PubMedCrossRefGoogle Scholar
  53. 53.
    Garchon H-J, Bedossa P, Eloy L, et al. Identification and mapping to chromosome 1 of a susceptibility locus for periinsulitis in non-obese diabetic mouse. Nature 353:260–2, 1991.PubMedCrossRefGoogle Scholar
  54. 54.
    Lander ES, Schork NJ. Genetic dissection of complex traits. Science 265:2037–48, 1994.PubMedCrossRefGoogle Scholar
  55. 55.
    Rodrigues N, Cornall R, Chandler P, et al. Mapping of an insulin-dependent diabetes locus, Idd-9, in NOD mice to chromosome 4. Mamm Genome 5:167–70, 1994.Google Scholar
  56. 56.
    Bell GI, Horita S, Karam JH. A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus. Diabetes 33:176–83, 1984.PubMedCrossRefGoogle Scholar
  57. 57.
    Julier C, Hyer R, Davies J, et al. Insulin-IGF2 region on chromosome lip encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility. Nature 354: 155–9, 1991.PubMedCrossRefGoogle Scholar
  58. 58.
    Bennett ST, Lucassen AM, Gough SCL, et al. Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene mini-satellite locus. Nature Genet 9:284–92, 1995.PubMedCrossRefGoogle Scholar
  59. 59.
    Rowe RE, Wapelhorst B, Bell Gl et al. Linkage and association between insulin-dependent diabetes mellitus (IDDM) susceptibility and markers near the glucokinase gene on chromosome 7. Nature Genet 10:240–2, 1995.PubMedCrossRefGoogle Scholar
  60. 60.
    Cordell HJ, Kawaguchi Y, Todd JA, Farrall M. An extension of the Maximum Lod Score method to X-linked loci. Ann Hum Genet 59:435–449, 1995.PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Boston 1996

Authors and Affiliations

  • Hiroshi Ikegami
    • 1
    • 3
  • Susumu Makino
    • 2
  • Toshio Ogihara
    • 1
  1. 1.Department of Geriatric MedicineOsaka University Medical SchoolOsakaJapan
  2. 2.Aburahi LaboratoriesShionogi & Co. Ltd.OsakaJapan
  3. 3.Department of Geriatric MedicineOsaka University Medical SchoolSuita, Osaka 565Japan

Personalised recommendations