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Résumé:
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The proteolipid protein (Plp) gene promoter is responsible for driving expression of one of the major components of myelin
– PLP and its splice variant DM-20. Both products are classically thought to express predominantly in oligodendrocytes.
However, accumulating evidence suggests Plp expression is more widespread than previously thought. In an attempt to
create a mouse model for inducing oligodendrocyte-specific gene deletions, we have generated transgenic mice expressing
a Cre recombinase cDNA under control of the mouse Plp promoter. We demonstrate Plp promoter driven Cre expression is
restricted predominantly to mature oligodendrocytes of the central nervous system (CNS) at postnatal day 28. However,
crosses into the Rosa26LacZ and mT/mG reporter mouse lines reveal robust and widespread Cre activity in neuronal tissues at
E15.5 and E10.5 that is not strictly oligodendrocyte lineage specific. By P28, all CNS tissues examined displayed high levels of
reporter gene expression well outside of defined white matter zones. Importantly, our study reinforces the emerging idea
that Plp promoter activity is not restricted to the myelinating cell lineage, but rather, has widespread activity both during
embryonic and early postnatal development in the CNS. Specificity of the promoter to the oligodendrocyte cell lineage, as
shown through the use of a tamoxifen inducible Plp-CreERt line, occurs only at later postnatal stages. Understanding the
temporal shift in Plp driven expression is of consequence when designing experimental models to study oligodendrocyte
biology. |
