Regulation of Cre Recombinase: Use of Ligand-Regulated and Dimerizable Cre for Transgenesis

Drug-regulatable site-specific recombinases have become, during the last decade, a central tool for �transgenesis. They allow, depending on the constructs used, the activation or inactivation of target genes in a time-dependent or, if combined with the use of a specific promoter, in a time- and cell-type-dependent manner. The most widely used approach to obtain this regulation relies on the fusion of the recombinase, mostly Cre recombinase, with the ligand-binding domain (LBD) of a steroid receptor, with the resulting Cre-LBD molecule regulated by the cognate steroid. Another, still experimental, method is based on the dimerization of two complementing inactive fragments of Cre, with the drug-induced or spontaneous association of the fragments leading to a reinstatement of the recombinase activity. These different approaches will be described, with a special emphasis on the practical aspects: choice and efficacy of the different variants, drug regimens, and potential pitfalls.