The NOD Idd9 genetic interval influences the pathogenicity of insulitis and contains molecular variants of Cd30, Tnfr2, and Cd137

Previous analyses of NOD mice have shown that some genes control the develo pment of both insulitis and diabetes, while other loci influence diabetes w ithout reducing insulitis. Evidence for the existence of a gene only influe ncing diabetes, ldd9 on mouse chromosome 4, is provided here by the develop ment of a novel congenic mouse strain, NOD.B10ldd9. NOD.B10ldd9 mice displa y profound resistance to diabetes even though nearly all develop insulitis. Subcongenic analysis has demonstrated that alleles of at least three B10 g enes, ldd9.1, ldd9.2, and ldd9.3 are required to produce ldd9-mediated diab etes resistance. Candidate genes with amino acid differences between the NO D and B10 strains have been localized to the 5.6 cM ldd9.2 interval (Tnfr2, Cd30) and to the 2.0 cM ldd9.3 interval (Cd137).