SUSCEPTIBILITY AND RESISTANCE LOCI IN MOUSE EAE

描述(改编自《研究者摘要》)：多发性硬化症(MS) 是人类中枢神经系统的主要炎症性疾病。两者都有 环境和遗传因素导致了据信 主要是免疫病理病因学。虽然环境因素是 在疾病发病机制中的重要作用，它们只能在 遗传上允许的寄主。黄曲霉毒素的鉴定及分子特征研究 实验性变态反应性脑脊髓炎的疾病易感基因， 多发性硬化症的基本动物模型，将有助于更好地理解 这些因素在免疫病理途径中的相互作用导致 疾病。推而广之，研究人员提出同源基因，或 它们所属途径中的其他基因也将与 对多发性硬化症的易感性这项研究的长期目标是 其应用是表征支配人类免疫系统的免疫调节基因 EAE在小鼠体内的表型表达。隔离、识别和研究 这些基因首先必须精确定位在编码的染色体上 这最好是使用分子基因组排除图谱来实现的 以DNA为基础的标记。在上一个供资期间，这种方法允许 研究人员将确定控制EAE的二元和数量性状基因座 易感性以及疾病的临床和组织病理学参数。 此外，他们还确定了独特的疾病亚型，与 人类多发性硬化症的临床过程，并概括了所见的性二型。 在BPHS的位置克隆方面也取得了实质性进展，并 EAE和自身免疫性疾病共同的自身免疫性疾病易感基因 炎。在此续订申请中，他们将：1)建立互惠， SJL/J与B10.S/DvTe小鼠表型选择的同源系 同时进行多世代回交连锁分析，以验证和 扩展他们对基因组扫描中确定的EAE基因座的分析和2) 完成BPHS基因的定位克隆。

DESCRIPTION (Adapted from the Investigator's Abstract): Multiple sclerosis (MS) is the major inflammatory disease of the central nervous system in humans. Both environmental and genetic factors contribute to what is believed to be primarily an immunopathologic etiology. Although environmental factors are important in disease pathogenesis, they can only exert their effects in genetically permissive hosts. Identification and molecular characterization of disease susceptibility genes in experimental allergic encephalomyelitis (EAE), the principle animal model of MS, will lead to a better understanding of the interplay between such factors in the immunopathologic pathways leading to disease. By extension, the investigators propose that homologous genes, or other genes in the pathways to which they belong, will also be relevant in susceptibility to MS. The long-term goal of the research proposed in this application is to characterize the immunoregulatory genes that govern the phenotypic expression of EAE in the mouse. To isolate, identify, and study these genes, they must first be precisely located on the chromosomes encoding them, this is best achieved using molecular genome exclusion mapping with DNA-based markers. During the previous funding period this approach allowed the investigators to identify binary and quantitative trait loci that control EAE susceptibility and the clinical and histopathologic parameters of the disease. Additionally, they identified unique disease subtypes that correlate with the clinical courses of human MS and recapitulated the sexual dimorphisms seen. Substantial progress was also made toward the positional cloning of Bphs, an autoimmune disease susceptibility locus common to both EAE and autoimmune orchitis. In this renewal application they will: 1) establish reciprocal, phenotype selected congenic lines between SJL/J and B10.S/DvTe mice and simultaneously do multi-generational backcross linkage analysis to verify and extend their analysis of the EAE loci identified in genome scans and 2) complete the positional cloning of Bphs.