Genetic and environmental control of diabetes induction by multi-dose streptozotocin in two BALB/c substrains.

BALB/cJ male mice were resistant and BALB/cByJ males were susceptible to induction of diabetes by multi-dose streptozotocin (MSz). Although both closely-related BALB/c substrains expressed H-2d haplotype, they could be differentiated by allelic differences at three genetic loci [Qa-2 (Chr 17), Bcd-1 (Chr 5), and Afr-1]. (BALB/cJ X BALB/cByJ)F1 males inherited the BALB/cJ resistance phenotype in a dominant fashion, thereby eliminating the BALB/cJ-expressed Afr-1b (recessive) allele as the susceptibility locus. Backcross of F1 mice to the susceptible BALB/cByJ strain produced a 1:1 segregation of susceptible and resistant (F1-like) phenotypes, suggesting that susceptibility was controlled by a single recessive gene. No linkage was found between the putative susceptibility gene and the mutant BALB/cByJ Qa-2,3 gene linked to the H-2 complex or with the mutant Bcd-1c allele. Since the resistant F1 males expressed low levels of androgen-dependent mouse urinary protein characteristic of the resistant BALB/cJ parental strain, the possibility was discussed that the alleles controlling sensitivity to MSz also controlled tissue sensitivity to endogenous androgens. An environmental effect on phenotype expression was indicated when BALB/cByJ males obtained from a colony free of pneumonia virus of mice (PVM) showed an attenuated rate of response to hyperglycemia induction in comparison to males obtained previously from an enzootically infected colony.