Purkinje cell-specific and inducible gene recombination system generated from C57BL/6 mouse ES cells

Spatiotemporally restricted gene targeting is needed for analyzing the func tions of various molecules in a variety of biological phenomena. We have ge nerated an inducible cerebellar Purkinje cell-specific gene targeting syste m. This was achieved by establishing a mutant mouse line (D2CPR) from a C57 BL/6 mouse ES cell line, which expressed a fusion protein consisting of the Cre recombinase and the progesterone receptor (CrePR). The Purkinje cell-s pecific expression of CrePR was attained by inserting CrePR into the glutam ate receptor delta2 subunit (GluR delta2) gene, which was expressed specifi cally in the Purkinje cells. Using the transgenic mice carrying the Cre-med iated reporter gene, we showed that the antiprogesterone RU486 could induce recombinase activity of the CrePR protein specifically in the mature cereb ellar Purkinje cells of the D2CPR line. Thus this mutant line will be a use ful tool for studying the molecular function of mature Purkinje cells by ma nipulating gene expression in a temporally restricted manner. (C) 2001 Acad emic Press.