Cutting edge: Homologous recombination of the MHC class IK region defines new MHC-Linked diabetogenic susceptibility gene(s) in nonobese diabetic mice

To localize the MHC-linked diabetogenic genes in the nonobese diabetic (NOD ) mouse, a recombinational hotspot from the B10.A(R209) mouse was introduce d to the region between the MHC class I K and class II A of the NOD mouse w ith the recombinational site centromeric to the Lmp2/Tap1 complex by breedi ng the two strains, Replacement of the NOD region centromeric to the recomb inational site with the same region in R209 mice prevented the development of diabetes (from 71 to 3%) and insulitis (from 61 to 15%) in the N7 intra- MHC recombinant NOD mice. Similarly, the replacement of the NOD class II A, E and class I D region with the same region in R209 mice prevented the dis eases (diabetes, from 71 to 0%; insulitis, from 61 to 3%). In addition to t he MHC class II genes, there are at least two MHC-linked diabetogenic genes in the region centromeric to Lmp2.