Epistatic modifiers of autoimmunity in a murine model of lupus nephritis

被引：150

作者：

Morel, L ^{[1
]}

Tian, XH

Croker, BP

Wakeland, EK

机构：

[1] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA

[2] Univ Florida, Coll Med, Ctr Mammalian Genet, Gainesville, FL 32610 USA

来源：

IMMUNITY | 1999年 / 11卷 / 02期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/S1074-7613(00)80088-6

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Sle1 and Sle3 are NZW-derived loci that mediate lupus nephritis on a C57BL/6 background. The absence of severe autoimmunity in NZW suggests that the NZW genome suppresses these genes. (B6.NZMc1[Sle1] x NZW)F1 hybrids develop severe humoral autoimmunity and fatal lupus nephritis, indicating that suppression of Sle1 from NZW is recessive. Linkage analysis identified four epistatic modifiers, Sles1-4, whose cumulative effect accounted for the benign autoimmunity in NZW. The specific suppression of Sle1 but not Sle2 or Sle3 by Sles1 was directly demonstrated via the production and analysis of bicongenic strains. Moreover, Sles1 was sufficient to completely suppress autoimmunity initiated by Sle1 in B6.NZMc1 x NZW hybrids. These results demonstrate the complex epistatic interactions of loci augmenting and suppressing systemic autoimmunity.

引用

页码：131 / 139

页数：9

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