HYPOMYELINATION IN TRANSGENICS--MODEL FOR PML

JC病毒（JCV）是一种在人类中广泛传播的人乳头状病毒

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.