A single dose of the MHC-linked susceptibility determinant associated with the RT1u haplotype is permissive for insulin-dependent diabetes mellitus in the BB rat.

Syndromes of insulin-dependent diabetes mellitus (IDDM) have been described in the mouse, in the rat and in man. In all three species, the presence of one or more specific alleles of the major histocompatibility complex is a prerequisite for the appearance of the disease. In the BB rat, diabetes is associated with the RT1u haplotype. We have performed a series of intercrosses of diabetic BB rats with normal Lewis and Buffalo rats and examined the offspring of all litters producing at least one diabetic animal. Forty-five of the 250 rats that developed diabetes were heterozygous for the RT1u haplotype by serotyping. Furthermore, the diabetic rats heterozygous by serotyping at the RT1A class I loci were also heterozygous at the RT1B and RT1D loci of the class II region and did not show evidence of a recombinant haplotype when examined by Southern blot analyses using molecular probes for class I and class II genes. Diabetic rats heterozygous or homozygous for RT1u were phenotypically indistinguishable with respect to age of onset and severity of disease. Therefore, in the rat, as in the human, a single dose of the high-risk allele at the major histocompatibility complex is sufficient for the development of IDDM if other susceptibility factors and the appropriate environmental factors are in place.