Encinas J A, Lees M B, Sobel R A, Symonowicz C, Greer J M, Shovlin C L, Weiner H L, Seidman C E, Seidman J G, Kuchroo V K
Center for Neurologic Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
J Immunol. 1996 Sep 1;157(5):2186-92.
Experimental autoimmune encephalomyelitis (EAE), a model for human multiple sclerosis, is a T cell-mediated autoimmune disease that can be induced in experimental animals by immunization with myelin Ags. Inbred strains of mice show varying degrees of susceptibility to EAE, indicating that susceptibility is an inherited trait. To define the genetic factors that control susceptibility to EAE, we performed linkage analysis on the first backcross (BC1) between highly susceptible SJL/J mice and resistant B10.S mice, both of which are of the H-2s haplotype. Mice were immunized for disease with encephalitogenic myelin proteolipid protein peptide 139 to 151, and analysis was performed on 68 backcross mice showing the severe disease phenotype (disease score > or = 3)and 68 backcross mice of the resistant phenotype (no clinical or histologic signs of disease) using microsatellite markers covering >98% of the genome. We found the strongest linkage (p = 0.001) with clinical disease at two loci: one at the telomeric end of chromosome 2, and another near the center of chromosome 3. In addition, several other regions showing some evidence of linkage (p < or = 0.05) with clinical disease were found.
实验性自身免疫性脑脊髓炎（EAE）是人类多发性硬化症的一种模型，是一种T细胞介导的自身免疫性疾病，可通过用髓鞘抗原免疫实验动物来诱发。近交系小鼠对EAE表现出不同程度的易感性，这表明易感性是一种遗传性状。为了确定控制EAE易感性的遗传因素，我们对高度易感的SJL/J小鼠和抗性B10.S小鼠（二者均为H-2s单倍型）之间的首次回交（BC1）进行了连锁分析。用致脑炎的髓鞘蛋白脂蛋白肽139至151对小鼠进行疾病免疫，并使用覆盖基因组>98%的微卫星标记，对68只表现出严重疾病表型（疾病评分≥3）的回交小鼠和68只抗性表型（无疾病临床或组织学迹象）的回交小鼠进行分析。我们在两个位点发现了与临床疾病最强的连锁（p = 0.001）：一个位于2号染色体的端粒末端，另一个位于3号染色体的中心附近。此外，还发现了其他几个与临床疾病有一些连锁证据（p≤0.05）的区域。
