MOLECULAR AND GENETIC STUDIES OF EAE IN COISOGENIC RATS

等基因大鼠 EAE 的分子和遗传学研究

• 批准号: 3410743
• 负责人: Elizabeth P Blankenhorn
• 金额: $ 10.93万
• 依托单位: HAHNEMANN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3410743
• 关键词: T cell receptor; T lymphocyte; alleles; autoimmune disorder; clone cells; disease /disorder model; experimental allergic encephalomyelitis; genetic disorder; genetic strain; genotype; histocompatibility gene; immune response genes; laboratory rat; major histocompatibility complex; molecular pathology

This research proposal is designed to elucidate genetic influences on the susceptibility of animals to experimentally induced autoimmune encephalomyelitis (EAE). Rat EAE is one of the best models for the human illness, multiple sclerosis. In both rats and man, these diseases are mediated by T lymphocytes, which escape from the normal constraints of self-tolerance and respond to a component of the central nervous system called myelin basic protein. In both species, major histocompatibility complex (MHC) genes contribute to the susceptibility of individuals for disease; however, it is known that other background genes also play a significant role. The identity of the background genetic influences is currently the subject of intense investigation. An excellent model in which to study genes (other than MHC loci) that govern CNS autoimmunity is the Lewis/Lewis-resistant (LER) rat combination. The non-susceptible LER rat is virtually co- isogenic with the highly susceptible Lewis rat, yet they share the same (susceptible) MHC haplotype. Our preliminary evidence shows that the T cell receptor beta chain loci are radically different between the two strains, and thus we propose that the T cell receptor gene complex has a major effect on the differential EAE-susceptibility of these two strains. Our studies have the potential to provide a rationale for the poorly understood heritability of multiple sclerosis, and to provide further insight into the mechanism of pathogenesis of this disease.

该研究建议旨在阐明遗传影响 关于动物对实验诱导的敏感性 自身免疫性脑脊髓炎（EAE）。 Rat Eae是最好的之一 人类疾病的模型，多发性硬化症。 在两只老鼠和 男人，这些疾病是由T淋巴细胞介导的，这些疾病逃脱了 从自我耐受的正常限制中，对 中枢神经系统的组成部分称为Myelin Basic 蛋白质。 在这两个物种中，主要的组织相容性复合物（MHC） 基因有助于个体对疾病的敏感性； 但是，众所周知，其他背景基因也发挥 重要作用。 背景遗传的身份 影响目前是严格调查的主题。 研究基因的出色模型（MHC基因座以外） 控制CNS自身免疫性是刘易斯/刘易斯耐药性（LER） 大鼠组合。 不敏感的ler大鼠实际上是共同的 与高度敏感的刘易斯大鼠的同源性，但它们共享 相同（易感）MHC单倍型。 我们的初步证据 表明T细胞受体β链基因座根本是 两种菌株之间的不同，因此我们提出 细胞受体基因复合物对差异有重大影响 这两种菌株的EAE敏感性。 我们的研究有 有可能为知之甚少的理由提供理由 多发性硬化症的遗传力，并提供进一步的见解 进入该疾病发病机理的机理。