LOCUS ON CHROMOSOME-18 COSEGREGATES WITH DIABETES IN THE BB OK RAT SUBLINE/

The spontaneously diabetic BB rat is a well-established animal model o f human insulin-dependent diabetes mellitus. Besides the lymphopenia g ene (Iddm 1) and the MHC class-II genes of the RT1(u) haplotype (Iddm 2, at least one other non-MHC gene (Iddm 3) is considered essential fo r diabetes development. To investigate the participation of this third gene in the development of diabetes in our BB/OK rat subline, we anal ysed 119 [(BB/OK x DA)F1 x BB/OK] first backcross hybrids phenotypical ly and genotypically. Genotyping with 5 classical and 28 polymorphic m icrosatellite markers indicated that the third gene is located on chro mosome 18, about 22 +/- 7 cM distal from the Olflocus (lod score = 2.3 3). Significantly more diabetics than Iddm 1 and Iddm 2 homozygous non diabetic subjects were homozygous for this focus. Interacting genes lo cated on chromosomes X and/or 1 seem to he involved.