Butterfield R J, Sudweeks J D, Blankenhorn E P, Korngold R, Marini J C, Todd J A, Roper R J, Teuscher C
Department of Veterinary Pathobiology, University of Illinois, Urbana 61802, USA.
J Immunol. 1998 Aug 15;161(4):1860-7.
Experimental allergic encephalomyelitis (EAE), the principal animal model of multiple sclerosis, is a genetically determined phenotype. In this study, analyses of the cumulative disease frequencies in parental, F1 hybrid, and F2 mice, derived from the EAE-susceptible SJL/J strain and the EAE-resistant B10.S/DvTe strain, confirmed that susceptibility to EAE is not inherited as a simple Mendelian trait. Whole genome scanning, using 150 informative microsatellite markers and a panel of 291 affected and 390 unaffected F2 progeny, revealed significant linkage of EAE susceptibility to marker loci on chromosomes 7 (eae4) and 17, distal to H2 (eae5). Quantitative trait loci for EAE severity, duration, and onset were identified on chromosomes 11 (eae6, and eae7), 2 (eae8), 9 (eae9), and 3 (eae10). While each locus reported in this study is important in susceptibility or disease course, interactions between marker loci were not statistically significant in models of genetic control. One locus, eae7, colocalizes to the same region of chromosome II as Orch3 and Idd4, susceptibility loci in autoimmune orchitis and insulin-dependent diabetes mellitus, respectively. Importantly, eae5 and eae7 are syntenic with human chromosomes 6p21 and 17q22, respectively, two regions of potential significance recently identified in human multiple sclerosis genome scans.
实验性自身免疫性脑脊髓炎（EAE）是多发性硬化症的主要动物模型，是一种由基因决定的表型。在本研究中，对源自EAE易感的SJL/J品系和EAE抗性的B10.S/DvTe品系的亲代、F1杂种和F2小鼠的累积疾病频率进行分析，证实EAE易感性并非作为简单的孟德尔性状遗传。使用150个信息丰富的微卫星标记以及一组由291只患病和390只未患病的F2后代组成的样本进行全基因组扫描，结果显示EAE易感性与7号染色体（eae4）和17号染色体上H2远端的标记位点存在显著连锁（eae5）。在11号染色体（eae6和eae7）、2号染色体（eae8）、9号染色体（eae9）和3号染色体（eae10）上鉴定出了EAE严重程度、病程和发病时间的数量性状位点。虽然本研究中报道的每个位点在易感性或疾病进程中都很重要，但在遗传控制模型中，标记位点之间的相互作用在统计学上并不显著。一个位点eae7与Orch3和Idd4定位于11号染色体的同一区域，分别是自身免疫性睾丸炎和胰岛素依赖型糖尿病的易感位点。重要的是，eae5和eae7分别与人染色体6p21和17q22同线，这是最近在人类多发性硬化症基因组扫描中确定的两个具有潜在重要意义的区域。
