A chimeric Cre recombinase inducible by synthetic,but not by natural ligands of the glucocorticoid receptor

Abstract

We have developed a new ligand-dependent chimeric recombinase (Cre-GR^dex) by fusing the site-specific Cre recombinase to the ligand binding domain (LBD) of a mutant human glucocorticoid receptor (GR^dex). The synthetic glucocorticoid receptor (GR) ligands dexamethasone, triamcinolone acetonide and RU38486 efficiently induce recombinase activity in F9 murine embryonal carcinoma cells expressing constitutively Cre-GR^dex. In contrast, no recombinase activity was detected in the absence of ligand or in the presence of the natural GR ligands corticosterone, cortisol or aldosterone. Moreover, physiological concentrations of these natural GR ligands do not affect Cre-GR^dex recombinase activity induced by dexamethasone. Thus, as previously shown using Cre-oestrogen receptor (ER) fusion proteins, Cre-GR^dex might be useful for achieving loxP site-directed mutagenesis in cultured cells and spatio-temporally controlled somatic cell mutagenesis in transgenic mice.