MHC-linked type 1 diabetes genes in NOD mice

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Type 1 diabetes is a polygenic autoimmune disease in man and the NOD mouse. The genes in the MHC region are the most important in determining susceptibility or resistance to type 1 diabetes. Replacement of (homologous recombination) of the NOD MHC class IK region with the R209 MHC class IK region prevented the development of diabetes and insulitis in the intra-MHC recombinant NOD mice. Similarly the replacement of the region of the NOD A, E and D with that of the R209 prevented the development of diabetes and insulitis. We have established six congenic lines with a homozygous segment of r209/r209 in the region of within 7.4 Mbp centromeric to the Lmp2-hotspot, and two congeniclines with homozygous segment of r209/r209 in the region of within 23 Mbp from the centromere. Our observation suggests that in addition to the MHC class II A there are four more MHC-linked type 1 diabetogenic genes in the 33.9 Mbp region centromeric to the Lmp2 gene, Idd1a, Idd1b, Idd1c and Idd1d. Our study aims to identify the four genes and examine their functions in the development of type 1 diabetes.