Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex.
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.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D005838:Genotype; D006720:Homozygote; D007328:Insulin; D008214:Lymphocytes / Q000473:pathology; D008285:Major Histocompatibility Complex; D008297:Male; D010179:Pancreas / Q000473:pathology; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF; D013577:Syndrome; D013997:Time Factors
D007328:Insulin