Abstract
Multiple low-dose of streptozotocin induces autoimmune diabetes in mice which is characterized by hyperglycemia with lymphocytic infiltration into the pancreatic islets. The influence of genetic background on the susceptibility to this experimental form of diabetes was studied by comparing the susceptibilities of various congenic resistant and recombinant strains with a B 10 background. On the basis of the results of the first experiment, animals were injected on five consecutive days with streptozotocin (40 mg/kg, i.p.). The mice were considered diabetic when non-fasting serum glucose levels were above 200 mg/dl.
In congenic resistant strains, mice from strains B 10. (H-2b) and B 10. BR (H-2k) showed high incidences of diabetes in response to streptozotocin treatment. However, mice from strains B 10. D 2 (H-2d) and B 10. S (H-2s) showed low incidences of diabetes. Therefore, it is suggested that the haplotypes b and k are high-susceptiblity alleles and that d and s are low-susceptibility alleles.
In congenic recombinant strains, mice with the same haplotype on the K, E, S and D loci in the H-2 complex showed different susceptibilities, indicating that the diabetic susceptibility genes are located outside the K, E, S and D loci.
Mice from strains with the high-responder haplotypes k and b on the A locus in the H-2 complex showed high incidences but mice with the low-responder alleles d and s showed low incidences. The results suggested that genes coding for susceptibility to diabetes are located in the A locus within the H-2 complex.
