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The first external domain of the nonobese diabetic mouse class II I-A beta chain is unique.
Proceedings of the National Academy of Sciences of the United States of America
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.
Amino Acid Sequence, Animals, Base Sequence, DNA/analysis, Diabetes Mellitus, Experimental/immunology, Genes, MHC Class II, Histocompatibility Antigens Class II/analysis, Macromolecular Substances, Major Histocompatibility Complex, Mice, Mice, Inbred Strains, Mice, Mutant Strains, Polymorphism, Restriction Fragment Length, Species Specificity
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