This review will focus on spontaneous autoimmune diabetes pathogenesis in NOD mice, although other models of beta cell destruction mediated by T cell receptor (TCR) transgenic T cells targeting ectopically expressed antigen such as in rat insulin promoter (RIP) driving lymphocytic choriomeningitis virus (21) RIP-membrane-bound form of ovalbumin (22) or insulin hemagglutinin (23) have contributed extensively to our understanding of T1D and are discussed elsewhere (24). This evidence concerns the gene INS and type 1 diabetes mellitus.