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

Abstract:

: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.

journal_name

Ann N Y Acad Sci

authors

Blankenhorn EP,Descipio C,Rodemich L,Cort L,Leif JH,Greiner DL,Mordes JP

doi

10.1196/annals.1394.020

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

128-31

eissn

0077-8923

issn

1749-6632

pii

annals.1394.020

journal_volume

1103

pub_type

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