The first external domain of the nonobese diabetic mouse class II I-A beta chain is unique.
The nonobese diabetic mouse is recognized as an important animal model for human insulin-dependent diabetes mellitus. One of the components of susceptibility to this disease has been mapped to the major histocompatibility complex. In this study, full-length cDNA clones encoding the I-A alpha and beta chains from the nonobese diabetic mouse have been isolated and sequenced. They are identical to the sequences previously determined from the H-2d haplotype except for the sequence encoding the first external domain, the leader peptide, and the 5' untranslated region of the I-A beta chain molecule. Most strikingly, there are five consecutive nucleotide substitutions which lead to two radical amino acid changes in a region that is conserved between human and mouse. We suggest that the unique structure of the first external I-A beta chain domain is a major determinant in the disease susceptibility that maps to the major histocompatibility complex of the nonobese diabetic mouse.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D012150:Polymorphism, Restriction Fragment Length; D013045:Species Specificity
D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D004247:DNA