An epistatic effect of the female specific loci on the development of autoimmune vasculitis and antinuclear autoantibody in murine lupus
An epistatic effect of the female specific loci on the development of autoimmune vasculitis and antinuclear autoantibody in murine lupus
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DOI：
10.1136/ard.2005.040832
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发表时间：
2005-09
影响因子：
27.4
通讯作者：
M-C Zhang;N. Misu;H. Furukawa;Y. Watanabe;M. Terada;H. Komori;T. Miyazaki;M. Nose;M. Ono
中科院分区：
文献类型：
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作者：
M-C Zhang;N. Misu;H. Furukawa;Y. Watanabe;M. Terada;H. Komori;T. Miyazaki;M. Nose;M. Ono
目的：研究狼疮鼠自身免疫性肾血管炎发病率和严重程度的基因位点。研究方法：对MRL/Mp-Faslpr（MRL/lpr）、C57 BL/6-Faslpr（B6/lpr）、（MRL/lpr×B6/lpr）F1和MRL/lpr×（MRL/lpr× B6/lpr）F1回交小鼠肾动脉血管炎进行组织病理学评价。利用回交小鼠的基因组DNA样本，基于多态性微卫星标记的基因型进行全基因组扫描、关联研究和连锁分析。血管炎等级和各种自身抗体水平的相关性也进行了评价。结果如下：MRL等位基因的两个隐性易感基因座分别位于4号和1号染色体上，先前被定义为自身免疫相关基因座，分别称为Arvm 1和Sle-1/Nba 2。前者以雌性特有的方式上位于后者。抗核自身抗体（ANA）IgG型滴度与血管炎分级显著相关，而抗核自身抗体IgM型滴度与血管炎分级无关，抗dsDNA IgG型滴度与血管炎分级无关。结论：本基因座已在以前的研究中使用一组不同的鼠株，表明它们是重要的发展中的自身免疫性血管炎的小鼠模型。自身免疫性血管炎和IgG抗核抗体的共存表明一个共同的遗传因素调节这些特征。
Objective: To identify the genetic loci regulating the incidence and severity of renal autoimmune vasculitis developed in murine lupus. Methods: Vasculitis of renal arteries was histopathologically evaluated in MRL/Mp-Faslpr (MRL/lpr), C57BL/6-Faslpr (B6/lpr), (MRL/lpr×B6/lpr) F1, and MRL/lpr×(MRL/lpr×B6/lpr) F1 backcross mice. Using genomic DNA samples of the backcross mice, genome-wide scans, association studies, and linkage analyses were carried out based on genotypes of polymorphic microsatellite markers. Correlations of vasculitis grade and levels of various autoantibodies were also evaluated. Results: Two recessive susceptibility loci of the MRL allele were identified on chromosomes 4 and 1, which had previously been defined as the autoimmune related loci termed Arvm1 and Sle-1/Nba2, respectively. The former was epistatic to the latter in a female specific manner. The titre of antinuclear autoantibody (ANA) in IgG class, but not ANA in IgM class or anti-dsDNA in either IgG or IgM class, correlated significantly with vasculitis grade. Conclusions: The present loci have been reported in previous studies using a different set of murine strains, suggesting that they are of importance in the development of autoimmune vasculitis in murine models. The concomitance of autoimmune vasculitis and IgG ANA suggests a shared genetic factor regulating these traits.