Genetic control of diabetes and insulitis in the nonobese diabetic mouse. Pedigree analysis of a diabetic H-2nod/b heterozygote.

The development of autoimmune type 1 diabetes mellitus in man and the nonobese diabetic (NOD) mouse is greatly influenced by a gene linked to the MHC. Although homozygosity at the NOD MHC is required for a high prevalence of disease, during backcross studies we have found a small number of diabetic H-2nod/b MHC heterozygotes. These diabetic heterozygotes could either represent a crossover event between the MHC and a putative MHC-linked diabetogenic gene or, alternatively, they could indicate that there is a dominant MHC-linked diabetic gene that has low penetrance in the heterozygous state. Pedigree analysis of a diabetic H-2nod/b MHC heterozygote favors the latter hypothesis.