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Low-dose streptozotocin-induced autoimmune diabetes is under the genetic control of the major histocompatibility complex in mice


In mice, an experimental autoimmune diabetes can be induced by multiple injections with low doses of streptozotocin. Since different mouse strains show a varying susceptibility towards this treatment, we have examined whether the experimental autoimmune diabetes is under the genetic control of the major histocompatibility complex (H-2 complex). Mice of five congenic resistant strains, differing in their genome only at the H-2 region, were identically treated on five consecutive days with 40 mg streptozotocin/kg body weight. Genes at the H-2 complex were found to determine the susceptibility towards the diabetogenic effect of streptozotocin: mice of H-2 haplotype k (B10.BR) developed persistent and strong hyperglycaemia (blood glucose approximately 17 mmol/1), mice of strain B10.A (H-2a), C57BL/10 (H-2b) and B10.D2 (H-2d) reacted with moderate hyperglycaemia (between 11.5 and 15.5 mmol/1), whereas mice of strain B10.S (H-2s) were resistant to the diabetogenic effect of low-dose streptozotocin except for a small and transient rise of blood glucose levels. It is concluded that genes within the major histocompatibility complex affect the diabetogenic response to multiple low-dose streptozotocin treatment.


  1. 1.

    Like AA, Rossini AA (1976) Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Science 193: 415–417

  2. 2.

    Like AA, Rossini AA (1978) Streptozotocin-induced pancreatic insulitis in mice. Morphological and physiological studies. Lab Invest 38: 470–486

  3. 3.

    Craighead JE (1978) Current views on the etiology of insulin-dependent diabetes mellitus. N Engl J Med 299: 1439–1445

  4. 4.

    Notkins AL (1977) Virus-induced diabetes mellitus. Arch Virol 54: 1–17

  5. 5.

    Cahill FC, McDevitt HO (1981) Insulin-dependent diabetes mellitus: the initial lesion. N Engl J Med 304: 1454–1465

  6. 6.

    Rossini AA, Williams RM, Appel MC, Like AA (1978) Complete protection from low-dose Streptozotocin-induced diabetes in mice. Nature 276: 182–184

  7. 7.

    Kiesel U, Freytag G, Biener J, Kolb H (1980) Transfer of experimental autoimmune insulitis by spleen cells in mice. Diabetologia 19: 516–520

  8. 8.

    Buschard K, Rygaard J (1977) Passive transfer of streptozotocin-induced diabetes mellitus with spleen cells. Acta path microbiol scand (Sect C) 85: 469–472

  9. 9.

    Beattie G, Lannom R, Lipsick J, Kaplan NO, Osler AG (1980) Streptozotocin-induced diabetes in athymic and conventional BALB/c mice. Diabetes 29: 146–150

  10. 10.

    Paik SG, Fleischer N, Shin SI (1980) Insulin-dependent diabetes mellitus induced by subdiabetogenic doses of streptozotocin: Obligatory role of cell-mediated autoimmune processes. Proc Nat Acad Sci USA 77: 6129–6133

  11. 11.

    Rossini AA, Appel MC, Williams RM, Like AA (1977) Genetic influence of the streptozotocin-induced insulitis and hyperglycemia. Diabetes 26: 916–920

  12. 12.

    Kiesel U, Greulich B, Marx-Soho Moumé C, Kolb H (1981) Induction of experimental autoimmune diabetes by low-dose streptozotocin treatment in genetically resistant mice. Immunol Letters 3: 227–230

  13. 13.

    Kiesel U, Kolb H, Freytag G (1981) Strain dependency of the transfer of experimental immune insulitis in mice. Clin Exp Immunol 43: 430–433

  14. 14.

    Kolb H, Kiesel U (1981) Localization of genes controlling an experimental model of human insulin-dependent diabetes mellitus within and outside the major histocompatibility complex. Immunobiol 160: 58–59 (Abstract)

  15. 15.

    Shand FL, Liew FY (1980) Differential sensitivity to cyclophosphamide of helper T cells for humoral responses and suppressor T cells for delayed-type hypersensitivity. Eur J Immunol 10: 480–483

  16. 16.

    Boucher DW, Hayashi K, Rosenthal J, Notkins AL (1975) Virus-induced diabetes mellitus. III. Influence of the sex and the strain of the host. J Infect Dis 131: 462–466

  17. 17.

    Yoon JW, Lesniak MA, Fussganger R, Notkins AL (1976) Genetic differences in susceptibility of pancreatic β cells to virus-induced diabetes mellitus. Nature 264: 178–180

  18. 18.

    Kromann H, Lernmark A, Yestergaard BF, Egeberg J, Nerup J (1979) The influence of the major histocompatibility complex (H-2) on experimental diabetes in mice. Diabetologia 16: 107–114

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Kiesel, U., Kolb, H. Low-dose streptozotocin-induced autoimmune diabetes is under the genetic control of the major histocompatibility complex in mice. Diabetologia 23, 69–71 (1982).

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Key words

  • H-2 dependence
  • experimental autoimmune diabetes
  • streptozotocin
  • genetic control
  • mice