There are well over 300 inbred mouse strains extant world-wide. Of these, only one, the nonobese diabetic (NOD) mouse, initially expected to be a normoglycemic strain [1] spontaneously develops an autoimmune, T-cell-mediated type 1 diabetes (T1D; former designation insulin-dependent diabetes mellitus, IDDM) syndrome. Considerable excitement was generated by initial genetic analysis of this strain. Sequencing of its MHC class II A chain allele revealed what initially was thought to be a unique (for mouse) sequence encoding a neutral serine instead of an aspartic acid (asp) residue at position 57 [2]. This finding of the ‘non-asp’substitution generated considerable excitement at the time because similar ‘non-asp’substitutions at residue 57 were reported in the ‘diabetogenic’human homologs (HLA-DQ alleles such as DQ0302)[2]. As will be noted below, it is not only the MHC class II region that contributes susceptibility in NOD mice, but rather, multiple loci in the extended haplotype. Since the MHC complex contains genes essential for antigen processing and presentation as well as for immune cell function, it was both satisfying and logical that the NOD MHC would be a primary determinant of T1D susceptibility. Initial genetic segregation analyses in which NOD was outcrossed with other inbred strains confirmed major diabetogenic contributions of the NOD MHC haplotype (H2g7). These early studies further suggested that only one or several