SUSCEPTIBILITY AND RESISTANCE LOCI IN EAE

描述：(摘自申请者摘要)：多发性硬化症(MS) 是中枢神经系统(CNS)的主要炎症疾病 在人类身上。环境和遗传因素都对 被认为主要是一种免疫病理病因。虽然 环境因素在疾病的发病机制中很重要，它们可以 只在基因允许的宿主身上发挥作用。 疾病易感性的鉴定和分子特征 实验性变态反应性脑脊髓炎(EAE)的基因 多发性硬化症的动物模型，将有助于更好地理解相互作用 在免疫病理途径中的这些因素之间导致 疾病。通过引申，我们提出同源基因或其他基因 在他们所属的道路上，也将与 这项研究的长期目标是多发性硬化症 Teuscher博士和Blankenhorn博士在此应用程序中的功能是 描述控制表型的免疫调节基因 EAE在小鼠体内的表达。为了隔离、识别和 要研究这些基因，首先必须将它们准确地定位在 对它们进行编码的染色体，这是利用分子基因组实现的最佳目标 利用DNA标记进行排斥性作图。为此， 调查人员将利用大型EAE表型分离的DNA 群体和先前定位的简单序列长度的面板 多态(SSLP)或微卫星。归根结底，调查结果 本申请中提出的研究将为以后的研究奠定基础 需要在分子水平上阐明两者之间的关系 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.