Abstract
We have previously reported studies of the association of gene products of the rat major histocompatibility complex (RT1) with DM in the rat. In crosses between the diabetic BB rat (RT1.AuBuDu and inbred Lewis (RT1.A1B1D1) or Buffalo (RT1.AbBbDb) rats, the presence of at least 1 u haplotype is a necessary but not sufficient condition for the development of DM. We have further reported that the Class II gene products (RT1.B and RI1.D) of the RT1 u haplotypes from DM rats do not differ from those of the inbred Wistar Furth (RT1.AuBuDu) rat. We now report on the segregation of diabetes in litters in which there were animals with more than one RT1 genotype and more than one rat with DM. Progeny from 10 mating pairs were examined; 6 were (u/u × u/x), 3 (u/x × u/x), and 1 (u/x × x/x) where x=RT1 allele other than u. 121 pups were typed at the RT1 A locus. There were 23 diabetics, 12 u/x and 11 u/u. In each litter, however, all of the diabetic sibs shared the same genotype. A recombination event between the Class I A locus and the Class II B and D loci was ruled out by mixed lymphocyte cultures. The results suggest that in addition to the requirement for at least 1 u haplotype, there may be a second gene conferring susceptibility to DM which is linked to RT1.
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