conditional transgenesis using dimerizable cre (dicre)有条件的转基因技术使用dimerizable cre(dicre).pdfVIP

Conditional Transgenesis Using Dimerizable Cre (DiCre) 1 2 3 2 4 1 Nicolas Jullien , Isabelle Goddard , Samia Selmi-Ruby , Jean-Luc Fina , Harold Cremer , Jean-Paul Herman * ´ ´ ´ ` 1 ICNE-UMR 6544 Centre National de la Recherche Scientifique (CNRS), Universite de la Mediterranee, Marseille, France, 2 Centre de Transgenese, ´ ´ ´ ´ ´ ´ Faculte de Medecine Nord, Institut Federatif de Recherche (IFR) Jean-Roche, Marseille, France, 3 INSERM UMR 664, Faculte de Medecine RTH Laennec, ´ ´ ´ ´ Universite Lyon I, Lyon, France, 4 IBDML-UMR 6216 Centre National de la Recherche Scientifique (CNRS), Universite de la Mediterranee, Marseille, France Cre recombinase is extensively used to engineer the genome of experimental animals. However, its usefulness is still limited by the lack of an efficient temporal control over its activity. We have recently developed a conceptually new approach to regulate Cre recombinase, that we have called Dimerizable Cre or DiCre. It is based on splitting Cre into two inactive moieties and fusing them to FKBP12 (FK506-binding protein) and FRB (binding domain of the FKBP12-rapamycin associated protein), respectively. These latter can be efficiently hetero-dimerized by rapamycin, leading to the reinstatement of Cre activity. We have been able to show, using in vitro approaches, that this ligand-induced dimerization is an efficient way to regulate Cre activit