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Ann N Y Acad Sci. 2007 Apr;1103:128-31. Epub 2007 Mar 21.

Refinement of the Iddm4 diabetes susceptibility locus reveals TCRVbeta4 as a candidate gene.

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Department of Microbiology and Immunology, Center for Immunogenetics and Inflammatory Diseases, Drexel University College of Medicine, Philadelphia, PA, USA.


Iddm4 is a dominant non-major histocompatibility complex (MHC) determinant of diabetes susceptibility in BBDR rats treated with poly I:C, plus depletion of regulatory T cells. In congenic MHC-identical normal WF rats, Iddm4(d) sensitively and specifically predicts induced diabetes. We report a new diabetes-susceptible subcongenic line that carries Iddm4 in a < 2.6 megabase interval. Candidate genes include the T cell receptor beta chain variable (TCRVbeta) family. We found that TCRVbeta4 in WF rats contains a stop codon, whereas 5/5 diabetes-susceptible rat strains express TCRVbeta4. We conclude that Iddm4-mediated diabetes resistance in rats may be due to a recessive protective mutation in TCRVbeta4.

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