Locus on chromosome 18 cosegregates with diabetes in the BB/OK rat subline

The spontaneously diabetic BB rat is a well-established animal model of human insulin-dependent diabetes mellitus. Besides the lymphopenia gene (Iddm 1) and the MHC class-II genes of the RT1u haplotype (Iddm 2), at least one other non-MHC gene (Iddm 3) is considered essential for diabetes development. To investigate the participation of this third gene in the development of diabetes in our BB/OK rat subline, we analysed 119 [(BB/OK x DA)F1 x BB/OK] first backcross hybrids phenotypically and genotypically. Genotyping with 5 classical and 28 polymorphic microsatellite markers indicated that the third gene is located on chromosome 18, about 22 +/- 7 cM distal from the Olf locus (Iod score = 2.33). Significantly more diabetics than Iddm 1 and Iddm 2 homozygous nondiabetic subjects were homozygous for this locus. Interacting genes located on chromosomes X and/or 1 seem to be involved.