Genes of SHR rats protect spontaneously diabetic BB/OK rats from diabetes:Lessons from congenic BB.SHR rat strains

Diabetes in BE rats share many common features with human type 1 diabetes. One of them is the complex and polygenic nature of disease. Analysis of cro ss hybrids of diabetic BB/OK rats and rats of different diabetes-resistant strains has demonstrated that beside the MHC genes, Iddm1 and the lymphopen ia, Iddm2 additional non-MHC genes are involved in diabetes development. To study the importance of the non-MHC genes, Iddm4 and Iddm3, two congenic B B.SHR rat strains were generated by recombining a segment of the SHR chromo some 6 (Iddm4; termed BB.6S; 15cM) or chromosome 18 (Iddm3; termed BB.18S; 24cM) into the BB/OK background by serial backcrossing and marker-aided sel ection. The characterization of both congenic strains demonstrates a drasti c reduction of diabetes frequency in comparison to the BB/OK strain (86% vs 14% and 34%). It is supposed that diabetes protective genes of SHR must be located on both chromosomal segments and that these suppress the action of the essential and most important genes of diabetes development in the BB/O K rat, Iddm1, and Iddm2. (C) 2001 Academic Press.