Segregation of autoimmune type 1 diabetes in a cross between diabetic BB and brown Norway rats

Diabetes-prone DP-BB rats spontaneously develop insulin-dependent diabetes mellitus resembling type 1 diabetes mellitus in man. Expression of T cell lymphopenia and presence of at least one class II major histocompatibility complex (MHC) RT1u haplotype are required for development of diabetes. Diabetes segregation was studied in lymphopenic backcross (BC) offspring from a cross between male DP-BB/HRI and female BN/Mol rats. Diabetes occurred in 75% of BC rats with genotype RT1u/u and in 18% of those being RT1n/u in genotype. The latter developed diabetes significantly later than MHC homozygotes and parental DP-BBs. Our data further point to the existence of additional genes of minor importance for development of IDDM. One of these seemed to be positioned on the X chromosome. The recently published linkage to chromosome 18 could not be confirmed however. Finally, the BN-derived non-albino allele of the C gene was associated with higher diabetes incidence. This points to the existence of minor susceptibility genes in other strains of rats.