The present address of Christopher L. Moore is CNS Pharmacology, Pfizer Global R & D, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.
Myelin proteolipid protein (Plp) intron 1 DNA is required to temporally regulate Plp gene expression in the brain
Article first published online: 18 SEP 2002
Journal of Neurochemistry
Volume 83, Issue 1, pages 193–201, October 2002
How to Cite
Li, S., Moore, C. L., Dobretsova, A. and Wight, P. A. (2002), Myelin proteolipid protein (Plp) intron 1 DNA is required to temporally regulate Plp gene expression in the brain. Journal of Neurochemistry, 83: 193–201. doi: 10.1046/j.1471-4159.2002.01142.x
- Issue published online: 18 SEP 2002
- Article first published online: 18 SEP 2002
- Received June 5, 2002; revised manuscript received July 15, 2002; accepted July 16, 2002.
- gene expression;
- Leydig cell;
- myelin proteolipid protein gene;
- spatiotemporal regulation;
- transgenic mice
The myelin proteolipid protein (Plp) gene encodes the most abundant protein found in mature CNS myelin. Expression of the gene is regulated spatiotemporally, with maximal expression occurring in oligodendrocytes during the myelination period of CNS development. Plp gene expression is tightly controlled. Misregulation of the gene in humans can result in the dysmyelinating disorder Pelizaeus-Merzbacher disease, and in transgenic mice carrying a null mutation or extra copies of the gene can result in a variety of conditions, from late onset demyelination and axonopathy, to severe early onset dysmyelination. In this study we have examined the effects of Plp intron 1 DNA in mediating proper developmental expression of Plp-lacZ fusion genes in transgenic mice. Our results reveal the importance of Plp intron 1 sequences in instigating the expected surge in Plp-lacZ gene activity during (and following) the active myelination period of brain development. Transgene expression was also detected in the testis (Leydig cells), however, the presence or absence of Plp intron 1 sequences had no effect on the temporal profile in the testis. Surprisingly, expression of the transgene missing Plp intron 1 DNA was always higher in the testis, ascompared to the brain, in all of the transgenic lines generated.