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.
Leiter
E H
EH
Jackson Laboratory, Bar Harbor, ME 04609.
Le
P H
PH
Prochazka
M
M
Worthen
S M
SM
Huppi
K
K
D000483:Alleles; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000503:physiopathology; D004198:Disease Susceptibility; D004334:Drug Administration Schedule; D004777:Environment; D008040:Genetic Linkage; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010641:Phenotype; D013045:Species Specificity; D013311:Streptozocin / Q000008:administration & dosage*
D013311:Streptozocin