Refinement of the Iddm4 diabetes susceptibility locus reveals TCRVbeta4 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, 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.
Blankenhorn
Elizabeth P
EP
Department of Microbiology and Immunology, Center for Immunogenetics and Inflammatory Diseases, Drexel University College of Medicine, Philadelphia, PA, USA.
Descipio
Cheryl
C
Rodemich
Lucy
L
Cort
Laura
L
Leif
Jean H
JH
Greiner
Dale L
DL
Mordes
John P
JP
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007135:Immunoglobulin Variable Region; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
D017931:DNA Primers; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta