EXPRESSION OF THE MYELIN BASIC-PROTEIN GENE IN TRANSGENIC MICE EXPRESSING HUMAN NEUROTROPIC VIRUS, JCV, EARLY PROTEIN

Transgenic mice containing the early region of the JC virus encoding T-antigen developed neurological disease resulting from dysmyelination in the central nervous system. In this study, we investigate expression of the myelin basic protein (MBP) gene, a major constituent of the myelin sheath, at the RNA level by Northern blot and S1 nuclease assay and at the protein level by Western blot analysis using anti-Map antibody in two distinct transgenic lines exhibiting different degrees of dysmyelination. Results from Western blot analysis of proteins from the brains of these mice revealed great reductions in MBP levels that parallel the severity of dysmyelination in the corresponding animals. Analysis of MBP RNA by Northern and quantitative S1 assays exhibited no alterations in the transcription initiation sites of the MBP gene in these animals; however, a significant decrease in the level of MBP mRNA was detected, suggesting that T-antigen may negatively influence transcription of the MBP gene. Results from Northern and Western blot analysis of proteolipid protein revealed low-level expression of this gene. Expression of JCV T-antigen is developmentally regulated in the transgenic mice; it appears at 8 days postnatal, peaks at 15 days, and substantially decreases in 18-day-old mice. The programmed expression of JCV T antigen, which overlaps with MBP gene transcription at the early stage of myelination, suggests the involvement of a pathway which modulates stage-specific regulation of myelin genes and viral gene expression in transgenic mice during brain development. (C) 1994 Academic Press, Inc.