Epistatic modifiers of autoimmunity in a murine model of lupus nephritis
Epistatic modifiers of autoimmunity in a murine model of lupus nephritis
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DOI：
10.1016/s1074-7613(00)80088-6
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发表时间：
1999-08-01
期刊：
影响因子：
32.4
通讯作者：
Wakeland, EK
中科院分区：
文献类型：
--
作者：
Morel, L;Tian, XH;Wakeland, EK
Sle1和Sle3是nzw衍生的基因座，在C57BL/6背景下介导狼疮性肾炎。NZW中缺乏严重的自身免疫表明，NZW基因组抑制了这些基因。(B6。NZMc1[Sle1] x NZW)F1杂交体产生严重的体液自身免疫和致死性狼疮肾炎，表明NZW对Sle1的抑制是隐性的。连锁分析鉴定出4个上位性修饰因子Sles1-4，其累积效应解释了NZW的良性自身免疫。通过双基因菌株的生产和分析，直接证明了Sles1对Sle1的特异性抑制作用，而对Sle2和Sle3没有特异性抑制作用。此外，Sles1足以完全抑制B6中由Sle1启动的自身免疫。NZMc1 x NZW杂交。这些结果证明了基因座增强和抑制系统性自身免疫的复杂上位性相互作用。
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.