Loci of the immune system are implicated in diabetes frequency and age at onset of diabetes in BB rats

The spontaneously diabetic BB rat is a well-established animal model in diabetes research developing an insulin-dependent type-1 diabetes mellitus closely resembling human diabetes. By several crossing studies using BB/OK rats it has been demonstrated that beside the MHC class-II genes of the RT1(u) haplotype, Iddm1, and the lymphopenia, Iddm2, at least two additional non-MHC genes located on chromosomes 6 (Iddm4) and 18 (Iddm3) are involved in diabetes development. In addition, there are at least three genes located on chromosomes 6 (Dm1), 8 (Dm2) and 10 (Dm3) influencing the age at onset of diabetes. Comparing the homologous regions between rat and human, it is shown that most diabetogenic genes lie on human chromosomes near genes involved in immune processes providing human geneticist with new candidate regions for the analysis of diabetogenic non-MHC genes in human type-1 diabetes.