NOD mice develop diabetes spontaneously (typically, in about 60%–90% of females and 20%–40% of males between the age of 12 to 30 weeks) reproducing many aspects of the human autoimmune disease (e.g., presence of islet-specific autoantibodies, inflammation of pancreatic islets, and dependence on MHC alleles), but also with some important differences such as more severe insulitis and gender bias. This evidence concerns the gene HLA-C and diabetes mellitus.