PRODUCTION OF CONGENIC MOUSE STRAINS CARRYING NOD-DERIVED DIABETOGENIC GENETIC INTERVALS - AN APPROACH FOR THE GENETIC DISSECTION OF COMPLEX TRAITS

Insulin-dependent (Type I) diabetes (IDD) in the NOD mouse is inherite d as a complex polygenic trait making the identification of susceptibi lity genes difficult. Currently none of the non-MHC IDD susceptibility genes in NOD have been identified. In this paper we describe the cong enic mouse approach that we are using for the dissection of complex tr aits, such as IDD. We produced a series of six congenic strains carryi ng NOD-derived diabetogenic genomic intervals, which were previously i dentified by linkage analysis, on a resistant background. These congen ic strains were produced for the purpose of characterizing the functio n of each of these genes, alone and in combinations, in IDD pathogenes is and to allow fine mapping of the NOD IDD susceptibility genes. Hist ological examination of pancreata from 6 to 8-month-old congenic mice reveals that intervals on Chromosomes (Chrs) 1 and 17, but not 3, 6, a nd 11, contain NOD-derived genes that can increase the trafficking of mononuclear cells into the pancreas. Insulitis was observed only very rarely, even in older congenic mice, indicating that multiple genes ar e required for this phenotype. These results demonstrate the utility o f this congenic approach for the study of complex genetic traits.