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/l), 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/l), 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.