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 expressio n of the myelin basic protein (MBP) gene, a major constituent of the m yelin sheath, at the RNA level by Northern blot and S1 nuclease assay and at the protein level by Western blot analysis using anti-Map antib ody in two distinct transgenic lines exhibiting different degrees of d ysmyelination. Results from Western blot analysis of proteins from the brains of these mice revealed great reductions in MBP levels that par allel the severity of dysmyelination in the corresponding animals. Ana lysis of MBP RNA by Northern and quantitative S1 assays exhibited no a lterations in the transcription initiation sites of the MBP gene in th ese animals; however, a significant decrease in the level of MBP mRNA was detected, suggesting that T-antigen may negatively influence trans cription of the MBP gene. Results from Northern and Western blot analy sis of proteolipid protein revealed low-level expression of this gene. Expression of JCV T-antigen is developmentally regulated in the trans genic mice; it appears at 8 days postnatal, peaks at 15 days, and subs tantially decreases in 18-day-old mice. The programmed expression of J CV T antigen, which overlaps with MBP gene transcription at the early stage of myelination, suggests the involvement of a pathway which modu lates stage-specific regulation of myelin genes and viral gene express ion in transgenic mice during brain development. (C) 1994 Academic Pre ss, Inc.