Centromeric interval of chromosome 4 derived from C57BL/6 mice accelerates type 1 diabetes in NOD.CD72b congenic mice

The nonobese diabetic (NOD) mouse is a useful model of autoimmune type 1 diabetes exhibiting many similarities to human type 1 diabetes patients including the presence of auto-reactive T cells and pancreas-specific autoantiboies. Multiple Idd loci control the development of diabetes in NOD mice. CD72, a B cell membrane-bound glycoprotein carrying a C-type lectin-like domain, is an inhibitory co-receptor of the B cell antigen receptor (BCR) that negatively regulates BCR signaling. Among four known haplotypes of mouse CD72, NOD mice carry the CD72c haplotype, whereas most of the other inbred strains of mice carry either CD72a or CD72b. In this study, we generated congenic NOD.CD72b mice that carry C57BL/6 (B6) mouse-derived centromeric chromosome 4 interval (24–45 cM) surrounding the CD72b locus. Unexpectedly, NOD.CD72b mice were not protected from diabetes, but rather exhibited accelerated development of both insulitis and diabetes. Our result defines novel locus or loci in the vicinity of CD72 gene that negatively control diabetes, indicating that NOD disease is under complex genetic controls of not only Idd genes but also disease-resistant genes.