SUSCEPTIBILITY AND RESISTANCE LOCI IN EAE

描述：（改编自申请人的摘要）：多发性硬化症（MS） 是中枢神经系统（CNS）的主要炎症性疾病 在人类身上。 环境和遗传因素都有助于什么 被认为主要是免疫病理学病因。 虽然 环境因素在疾病发病机制中很重要，它们可以 只在基因允许的宿主中发挥作用。 疾病易感性的鉴定和分子表征 实验性变态反应性脑脊髓炎（EAE）的基因，原理 MS的动物模型，将导致更好地了解相互作用 这些因素在免疫病理学途径中导致 疾病 通过延伸，我们提出同源基因，或其他基因， 在他们所属的途径中，也将与 对MS的易感性。 Drs. Teuscher和Blankenhorn在本申请中在功能上 表征控制表型的免疫调节基因， EAE在小鼠中的表达。 为了分离，识别， 研究这些基因，首先必须将它们精确定位在 编码它们的染色体，这一目标最好通过分子基因组来实现 基于DNA标记的排除作图。 为此， 研究者将利用来自大的EAE表型分离的DNA， 先前绘制的简单序列长度的群体和面板 多态性（SSLP）或微卫星。 最终， 本申请中提出的研究将奠定基础 需要在分子水平上阐明 新的免疫调节基因及其作用机制， 在神经免疫学领域。

DESCRIPTION: (Adapted from Applicant's Abstract): Multiple sclerosis (MS) is the major inflammatory disease of the central nervous system (CNS) 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, we propose that homologous genes, or other genes in the pathways to which they belong, will also be relevant to susceptibility to MS. The long-term goal of the research proposed by Drs. Teuscher and Blankenhorn in this application is to functionally characterize the immunoregulatory genes which govern the phenotypic expression of EAE in the mouse. In order to isolate, identify, and study these genes, they must first be precisely located on the chromosomes encoding them, a goal best achieved using molecular genome exclusion mapping with DNA-based markers. Towards this end, the investigators will utilize DNA from large EAE phenotyped segregating populations and panels of previously mapped simple sequence length polymorphisms (SSLPs) or microsatellites. Ultimately, the findings of the research proposed in this application will lay the foundation required to elucidate, at the molecular level, the relationships between novel immunoregulatory genes and their mechanisms of action, particularly in the area of neuroimmunology.