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 环境和遗传因素导致了 主要是免疫病理学病因。虽然环境因素 在疾病发病机制中起重要作用，它们只能在 基因许可的宿主的鉴定和分子表征 实验性变态反应性脑脊髓炎（EAE）中的疾病易感基因， MS的原理动物模型，将导致更好地理解 这些因素在免疫病理学途径中的相互作用导致 疾病通过扩展，研究人员提出同源基因，或 它们所属的途径中的其他基因也将与 对MS的易感性。本研究提出的长期目标是 应用是表征控制免疫系统的免疫调节基因。 EAE在小鼠中的表型表达。分离、鉴定和研究 这些基因，它们必须首先精确定位在染色体上， 这是最好的实现使用分子基因组排除作图， DNA标记。在上一个供资期间，这种方法使 研究人员确定控制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，他们还确定了与糖尿病相关的独特疾病亚型。 人类MS的临床过程，并概括了所见的性二型性。 Bphs的定位克隆也取得了实质性进展， EAE和自身免疫性疾病共同的自身免疫性疾病易感性位点 睾丸炎在此更新申请中，他们将：1）建立互惠， 表型选择SJL/J和B10.S/DvTe小鼠之间的同源系， 同时进行多代回交连锁分析验证， 扩展他们对基因组扫描中鉴定的EAE基因座的分析，以及2） 完成Bphs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.