The influence of genetic background on the expression of mutations at the diabetes locus in the mouse. III. Effect of H-2 haplotype and sex.
The expression of the mouse mutation, diabetes (db), was examined on eight different inbred genetic backgrounds. The influence of H-2 haplotype and sex was examined. Mice of both sexes in two diabetes (db) strains (C57BL/6J, 129/J) having the H-2b haplotype were resistant to the diabetogenic action of the mutant gene. On the contrary, two H-2d congenic diabetes stocks (C57BL/KsJ, DBA/2J) exhibited severe diabetes associated with beta-cell necrosis. However, diabetes resistance was not restricted to mice with H-2b haplotype since the congenic diabetes MA/J stock (H-2k) was also resistant. Similarly, diabetes susceptibility was not restricted to mice with the H-2d haplotype, since males, but generally not females, in the congenic CBA/Lt-db/db and C3HeB/FeJ-db/db stocks (both H-2k) also exhibited a severe diabetes. Males of the congenic SWR/J-db stock (H-2q) had a diabetes of intermediate severity. Female diabetes mice with H-2k and H-2q haplotypes exhibited a sustained hypertrophy and hyperplasia of beta-cells and were able to control hyperglycemia better than males. Thus, while the H-2b haplotype remains associated with resistance, and the H-2d haplotype with susceptibility to induction of genetic diabetes, the diabetes stocks with H-2k haplotype clearly illustrate the importance of non-H-2, but sex-associated, genetic modifiers.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000401:mortality; D005260:Female; D005786:Gene Expression Regulation; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000473:pathology; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D012737:Sex Factors; D013045:Species Specificity
D001786:Blood Glucose; D007328:Insulin