Selective ablation of an astroglial subset by toxic gene expression driven by tenascin promoter

In vitro culture, one of the astroglia-derived extracellular matrix proteins, tenascin, expressed highly in fibrous astrocytes, whereas it expressed only low levels in protoplasmic astrocytes. We devised a method of selectively altering the population of astroglial subsets in primary culture of astrocytes derived from embryonic mouse brains using toxic gene expression driven by the tenascin promoter.

We have identified that the segment of 512-bases of 5'-flanking plus 243-bases leader sequences of the mouse tenascin gene contains maximum promoter activity in primary culture of astrocytes by deletion analysis of 5'-upstream region. This promoter element was used to specifically express the herpes simplex virus thymidine kinase (HSV-TK) gene in tenascin-positive astrocytes.

This strategy allowed us to selectively decrease tenascin-positive astrocytes at the optimal concentration of ganciclovir, which is cytotoxic in HSV-TK-expressing cells.

This approach should be useful for examining the role of the tenascin-negative astroglial subset in the development and regeneration of the central nervous system.