1. ¹Department of Dentistry, University of Rochester School of Medicine & Dentistry, 625 Elmwood Avenue, Rochester, New York 14620, USA
2. ²Department of Neurobiology & Anatomy, University of Rochester School of Medicine & Dentistry, 625 Elmwood Avenue, Rochester, New York 14620, USA
3. ³Department of Neurology, Center for Aging & Developmental Biology, Aab Institute of Biomedical Science, University of Rochester, Rochester, New York 14642, USA

Correspondence: Stephanos Kyrkanides, Eastman Dental Center, 625 Elmwood Avenue, Rochester, NY 14620, USA. E-mail: Stephanos_Kyrkanides@urmc.rochester.edu

Received 17 July 2003; Accepted 31 July 2003.

Abstract

Genetic studies often require the employment of an inducible expression system, whereby the expression of a particular gene can be regulated by the exogenous administration of an inert ligand. Cre/loxP-based systems have been previously described as the basis for inducible expression systems by exerting site-specific DNA recombination. In our effort to enhance the properties of the RU486-responsive CrePr1 construct, we have developed the dual GLVP/CrePr system, in which RU486 confers activity control at both the transcriptional and the posttranslational level of CrePr1. This was achieved by placing CrePr1 transcriptional regulation under the control of the RU486-sensitive chimeric regulator GLVP. Stable cell lines harboring the dual GLVP/CrePr as well as the single CrePr1 system were developed. Our results indicate that the dually regulated system is highly inducible by RU486 while maintaining minimal basal activity ("leakage"), characteristics that can be employed in the development of transgenic mice in which genetic pathways can be turned on or turned off after exogenous administration of RU486 at physiologically inert doses.