Refinement of the Iddm4 Diabetes Susceptibility Locus Reveals TCRVβ4 as a Candidate Gene

:  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, Iddm4d sensitively and specifically predicts induced diabetes. We report a new...

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Published in:Annals of the New York Academy of Sciences 2007-04, Vol.1103 (1), p.128-131
Main Authors: BLANKENHORN, ELIZABETH P., DESCIPIO, CHERYL, RODEMICH, LUCY, CORT, LAURA, LEIF, JEAN H., GREINER, DALE L., MORDES, JOHN P.
Format: Article
Language:English
Subjects:
BB rat
genetics
Iddm4
QTL
T cell receptor
type 1 diabetes
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Summary::  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, Iddm4d 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 β chain variable (TCRVβ) family. We found that TCRVβ4 in WF rats contains a stop codon, whereas 5/5 diabetes‐susceptible rat strains express TCRVβ4. We conclude that Iddm4‐mediated diabetes resistance in rats may be due to a recessive protective mutation in TCRVβ4.
ISSN:0077-8923
1749-6632
DOI:10.1196/annals.1394.020