Iddm4糖尿病易感性位点的精细定位揭示TCRVbeta4为候选基因。

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

作者信息

Blankenhorn Elizabeth P, Descipio Cheryl, Rodemich Lucy, Cort Laura, Leif Jean H, Greiner Dale L, Mordes John P

机构信息

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

出版信息

Ann N Y Acad Sci. 2007 Apr;1103:128-31. doi: 10.1196/annals.1394.020. Epub 2007 Mar 21.

DOI:10.1196/annals.1394.020

PMID:17376830

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.

摘要

Iddm4是在用聚肌胞苷酸处理的BBDR大鼠中，加上调节性T细胞耗竭后，糖尿病易感性的主要非主要组织相容性复合体（MHC）决定因素。在同基因MHC相同的正常WF大鼠中，Iddm4(d)灵敏且特异地预测诱导性糖尿病。我们报告了一个新的糖尿病易感亚同基因系，其在小于2.6兆碱基的区间内携带Iddm4。候选基因包括T细胞受体β链可变区（TCRVβ）家族。我们发现WF大鼠中的TCRVβ4含有一个终止密码子，而5/5糖尿病易感大鼠品系表达TCRVβ4。我们得出结论，大鼠中Iddm4介导的糖尿病抗性可能归因于TCRVβ4中的一个隐性保护性突变。