A single major gene controls most of the difference in susceptibility to streptozotocin-induced diabetes between C57BL/6J and C3H/HeJ mice.

To assess genetic factors determining sensitivity to streptozotocin-induced diabetes in inbred strains of mice, a genetic analysis of streptozotocin-sensitive C57BL/6J and streptozotocin-resistant C3H/HeJ mice was performed. One week after a single dose of streptozotocin (200 mg/kg body weight), differences in plasma glucose concentration were marked between male mice of the C57BL/6J and C3H/HeJ strains (p less than 0.001). To determine the number of genes responsible for the difference, F1 male progeny of a cross between parental strains were produced, and found to be streptozotocin resistant like C3H/HeJ parents. F1 mice were, therefore, backcrossed with streptozotocin-sensitive C57BL/6J mice (Backcross: F1 female female X C57BL/6J male male). The plasma glucoses of backcrossed male mice (n = 41) following streptozotocin treatment appeared to segregate into two populations, half like the C57BL/6J parent, and half like the F1 parent. Statistical analysis of the data revealed that the data fit a model with two distributions better than one with a single distribution, suggesting a single major gene responsible for the difference in streptozotocin susceptibility. This hypothesis was also supported by the observation that streptozotocin sensitivity in 12 recombinant inbred strains of C57BL/6J and C3H/HeJ mice appeared to segregate into two classes. Resistance to streptozotocin induced diabetes in F1 mice suggested that the expression of this gene is recessive, although X-chromosome linked inheritance could not be excluded. Efforts to map the streptozotocin-sensitivity gene revealed lack of right linkage to several loci including the H-2 locus.(ABSTRACT TRUNCATED AT 250 WORDS)