HYPOMYELINATION IN TRANSGENICS--MODEL FOR PML

JC病毒（JCV）是一种在人类中广泛存在的人类乳多空病毒 人口。 感染通常发生在儿童时期， 是亚临床的 然而，在少数患者中， 免疫力受到疾病、遗传疾病或 在治疗中，JC被认为是致命的 进行性多灶性白质脑病 （PML）。 虽然PML是罕见的，但发病率有所上升 最近，由于大量的免疫功能低下的艾滋病患者 患者 JC病毒颗粒可以从脑损伤中分离出来， PML患者，其中存在异常少突胶质细胞 和星形胶质细胞。 脱髓鞘是由于 少突胶质细胞，中枢神经系统的髓鞘生成细胞， 神经系统 含有早期区域的转基因小鼠 JC病毒已经产生，两个品系的小鼠具有 中枢神经系统的髓鞘形成障碍。 这些小鼠 从而为这种人类脱髓鞘提供了一种动物模型 疾病 预计对转基因小鼠的分析将 导致对PML中涉及的生化过程的深入了解。 对这些小鼠的初步分析表明， 少突胶质细胞 其他小鼠携带天然存在的 将产生JC变体，并将分析小鼠，以 确定组织和发育的特定模式， JCV早期区域的表达。 髓鞘分析 髓鞘碱性蛋白（MBP）、蛋白脂质蛋白 (PLP)，髓鞘相关糖蛋白（MAG）将被 执行。 对于MBP和PLP，表达将在 在RNA和蛋白质水平上的几个发展阶段。 对于MAG，当核酸探针不可用时，表达 将仅限于蛋白质水平。 将试图 鉴定和分离结合并调节 JC早期区域的表达。 据估计， 这些相同的因子也将调节髓磷脂的表达- 特定蛋白质

JC virus (JCV) is human papovavirus that is widespread in human populations. Infections usually occur in childhood and normally are subclinical. However, in a small number of patients whose immunity has been compromised by disease, genetic disorders, or therapy, JC has been implicated as a causative agent in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). Although PML is rare, the incidence has risen somewhat recently because of the large pool of immuno-compromised AIDS patients. JC viral particles can be isolated from brain lesions of patients with PML, in which there are abnormal oligodendrocytes and astrocytes. Demyelination is caused by destruction of oligodendrocytes, the myelin-producing cells of the central nervous system. Transgenic mice containing the early region of JC virus have been generated, and two lines of mice have a dysmyelination in the central nervous system. These mice therefore provide an animal model for this human demyelinating disease. It is anticipated that analyses of the transgenic mice will lead to insight into the biochemical processes involved in PML. Initial analyses of these mice demonstrated expression in oligodendrocytes. Additional mice harboring naturally occurring JC variants will be generated and mice will be analyzed to determine the tissue- and development-specific patterns of expression of the JCV early regions. Analyses of the myelin specific proteins myelin basic protein (MBP), proteo-lipid protein (PLP), and myelin-associated glycoprotein (MAG) will be performed. For MBP and PLP, expression will be determined at several stages of development at both the RNA and protein levels. For MAG, where a nucleic acid probe is not available, expression will be limited to the protein level. Attempts will be made to identify and isolate protein factors that bind to, and regulate expression of, the JC early region. It is anticipated that some of these same factors also will regulate expression of the myelin- specific proteins.