Genetic control of autoimmune myocarditis mediated by myosin-specific antibodies
Genetic control of autoimmune myocarditis mediated by myosin-specific antibodies
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DOI：
10.1007/s002510050466
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发表时间：
1999-02-01
期刊：
影响因子：
3.2
通讯作者：
Kotzin, BL
中科院分区：
文献类型：
--
作者：
Kuan, AP;Chamberlain, W;Kotzin, BL
自身免疫性疾病既包括自身反应性的发展，也包括器官损伤的表达，其易感性在遗传上是复杂的。我们最近报道了自身免疫性心肌炎对抗体介导的心脏损伤的易感性是菌株特异性的。DBA/2小鼠在给予肌球蛋白特异性抗体后发生心肌炎，而BALB/c小鼠则没有。这种易感性似乎受心肌细胞外基质中肌球蛋白的表达控制。CByD2F1小鼠对心肌炎的诱导均具有抗性，并且不显示细胞外肌球蛋白，这表明这些性状具有隐性遗传成分。对DBA/2 x CByD2F1小鼠的易感性进行回交分析，发现12号染色体上的一个位点与心肌炎密切相关。在雄性小鼠中，1号染色体上的第二个区域也与疾病易感性有关。然而，雌性和雄性小鼠的遗传易感性在遗传上是复杂的。本研究表明，组织损伤的遗传基础可以与自身反应性的遗传基础分开分析，未来的研究将确定本研究确定的遗传因素是否也与风湿热易感性有关。
Autoimmune disease involves both the development of autoreactivity and the expression of organ damage, and susceptibility is genetically complex. We recently reported that in autoimmune myocarditis susceptibility to antibody-mediated cardiac injury is strain specific. DBA/2 mice develop myocarditis following administration of myosin-specific antibody, while BALB/c mice do not. This susceptibility appears to be controlled by expression of myosin in the myocardial extracellular matrix. CByD2F1 mice are both resistant to induction of myocarditis and do not demonstrate extracellular myosin indicating a recessive genetic component to these traits. A backcross analysis of susceptibility using DBA/2 x CByD2F1 mice revealed a locus on chromosome 12 that is strongly linked with myocarditis, In male mice there was a second region on chromosome 1 that also contributes to disease susceptibility. However, genetic susceptibility in both female and male mice was genetically complex. This study demonstrates that the genetic basis of tissue injury can be analyzed separately from the genetic basis of autoreactivity, Future studies will determine whether the genetic factors identified in this study are also involved in susceptibility to rheumatic fever.