Faculty Research 1980 - 1989

Genetic control of pathogenesis of diabetes in C3H mice. Influence of the major histocompatibility complex.

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Blood-Glucose: an, Body-Weight, Diabetes-Mellitus-Experimental: fg, Disease-Susceptibility, Female, Genotype, H-2-Antigens: ge, Major-Histocompatibility-Complex, Male, Mice, Mice-Inbred-C3H: ge, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

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Diabetes. 1984 Nov; 33(11):1068-71.


AM17631, AM27722


Inbred strains of genetically diabetic (db/db) male mice with H-2b haplotype were heretofore found resistant to the diabetogenic action of the db mutation, whereas C3HeB/FeJ-db/db males with H-2k haplotype were susceptible. To determine whether the major histocompatibility complex was linked to diabetes predisposition, we mated C3H.SW/SnJ females (H-2b haplotype) with C3HeB/FeJ- +/db males, identified the +/db heterozygotes in the F1 generation (all H-2b/H-2k), and intercrossed these to produce F2 db/db male offspring that were classed and studied according to the three segregating H-2 genotypes. We found an accelerated diabetes pathogenesis in terms of early onset of severe hyperglycemia, destruction of pancreatic beta cells, and mortality that was not linked to H-2. Of 9 F2 male diabetics with H-2b/H-2b genotype, 14 with H-2b/H-2k genotype, and 5 with H-2k/H-2k genotype, all showed a more severe syndrome than did the grandparental-type C3HeB/FeJ-db/db males. We conclude that on the C3H inbred background, the major histocompatibility complex is not a major background modifier of the diabetes syndrome. The complexity of the results suggests residual non-H-2-related genetic variance between the two grandparental C3H stocks, with C3H.SW/SnJ females possessing diabetes susceptibility factors apparently lacking in C3HeB/FeJ (a stock bred to be free of the milk-borne mouse mammary tumor virus). Since C3H.SW/SnJ females transmitted to F2 males unknown diabetogenic factor(s) that did not appear to segregate, inheritance of a virus was suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

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