A syndrome of spontaneous diabetes mellitus has been previously described in a partially inbred rat strain called BB Wistar. We have determined whether there is major histocompatibility complex (MHC) linkage as well as other predisposing haplotype-associated factors of development. BB rats are RT1 (MHC) genotype u/u. Using BB x Lewis F1 hybrid matings, an F2 study analyzed 128 rats from 8 primary and 3 additional litters from a breeding pair producing a diabetic offspring. 4 of 128 F2 rats, all from the 48 progeny of same breeding pair, became clinically diabetic. The four diabetics were all genotype u/u (P = 0.03). In the primary F2 litters, haplotype distribution was not different from the 1:2:1 expected ratio. However, in the four litters from the from the F1 breeding pair producing diabetics, there was an increased number of u/u animals. Two-way analysis of variance revealed significant differences in pancreatic insulin content between litters (diabetics excluded), P less than 0.001, and between haplotypes P less than 0.007 with heterozygous u/u less than 1/1 progeny. The glucagon content showed no significant differences. These data demonstrate (a) MHC linkage with spontaneous diabetes in this rat model; (b) penetrance similar to the human disease; and (c) a possible association of MHC haplotype with pancreatic inflammation as well as insulin content in nondiabetic F2 siblings.
Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex.
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E Colle, R D Guttmann, T Seemayer; Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex.. J Exp Med 1 October 1981; 154 (4): 1237–1242. doi: https://doi.org/10.1084/jem.154.4.1237
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