SEGREGATION OF AUTOIMMUNE TYPE-1 DIABETES IN A CROSS BETWEEN DIABETICBB AND BROWN-NORWAY RATS

Diabetes-prone DP-BB rats spontaneously develop insulin-dependent diab etes mellitus resembling type 1 diabetes mellitus in man. Expression o f T cell lymphopenia and presence of at least one class II major histo compatibility complex (MHC) RT1(u) haplotype are required for developm ent of diabetes. Diabetes segregation was studied in lymphopenic backc ross (BC) offspring from a cross between male DP-BB/HRI and female BN/ Mol rats. Diabetes occurred in 75% of BC rats with genotype RT1(u/u) a nd in 18% of those being RT1(u/u) in genotype. The latter developed di abetes significantly later than MHC homozygotes and parental DP-BBs. O ur data further point to the existence of additional genes of minor im portance 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 all ele of the C gene was associated with higher diabetes incidence. This points to the existence of minor susceptibility genes in other strains of rats. (C) 1997 Academic Press Limited.