Autosomal loci associated with a sex‐related difference in the development of autoimmune phenotypes in a lupus model
Autosomal loci associated with a sex‐related difference in the development of autoimmune phenotypes in a lupus model
复制标题
DOI：
10.1002/eji.200637016
复制
发表时间：
2007-10
影响因子：
5.4
通讯作者：
N. Misu;Ming-Cai Zhang;S. Mori;T. Miyazaki;H. Furukawa;Takeshi Sasaki;M. Nose;M. Ono
中科院分区：
文献类型：
--
作者：
N. Misu;Ming-Cai Zhang;S. Mori;T. Miyazaki;H. Furukawa;Takeshi Sasaki;M. Nose;M. Ono
性别相关差异（SrD）是人类自身免疫性疾病的一般特征。越来越多的证据表明性激素和自身免疫性疾病之间存在联系。在这里，通过使用狼疮小鼠模型的遗传方法，我们试图显示遗传因素参与自身免疫性疾病中SrD的发展。利用MRL/lpr ×（MRL/lpr × C57 BL/6.Faslpr）F1（MBN 2）小鼠全基因组搜索MRL/Mp.Faslpr（MRL/lpr）品系小鼠自身免疫表型的连锁位点，该品系小鼠表现为肾小球肾炎、脾肿大和抗核自身抗体。全基因组关联研究证实了4、7、13和17号染色体上的4个连锁位点。此外，使用雄性和雌性MBN 2小鼠组进行的差异分析显示，位于染色体4（41-72 cM，MRL/lpr等位基因）和7（4-21 cM，B6/lpr等位基因）上的两个基因座是雄性特异性的和抑制的自身免疫表型。值得注意的是，两个基因座的总和效应充分解释了MBN 2小鼠中出现的一系列SrD。我们目前的研究结果表明，在自身免疫性SrD的发展中存在男性主导的机制，这取决于常染色体基因座在未定义的男性特异性条件下的作用。
Sex‐related differences (SrD) are a general characteristic of human autoimmune diseases. There is an increasing body of evidence that suggests a link between sex‐related hormones and autoimmune onsets. Here, through a genetic approach using a lupus mouse model, we attempted to show the involvement of genetic factors in the development of SrD in autoimmune diseases. Using MRL/lpr × (MRL/lpr × C57BL/6.Faslpr)F1 (MBN2) mice, the whole genome was searched to identify linkage loci to autoimmune phenotypes inherited from a lupus MRL/Mp.Faslpr (MRL/lpr) strain of mice, which exhibits glomerulonephritis, splenomegaly and antinuclear autoantibody. The genome‐wide association study confirmed four linkage loci on chromosomes 4, 7, 13, and 17. Furthermore, differential analyses performed using male and female groups of MBN2 mice revealed that two loci located on chromosomes 4 (41–72 cM, MRL/lpr allele) and 7 (4–21 cM, B6/lpr allele) were male specific and suppressed autoimmune phenotypes. Notably, the sum effect of the two loci adequately explained a range of SrD developed in the MBN2 mice. Our present findings suggest the presence of a male‐predominant mechanism underlying the development of SrD in autoimmunity, depending on the effects of autosomal loci under an undefined male‐specific condition.