Timing Is Everything in Life

Conditional Transgene Expression in the Cardiovascular System

From the Albert Einstein College of Medicine, Bronx, NY.

Correspondence to Glenn I. Fishman, MD, Cardiovascular Institute, Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1269, New York, NY 10029-6574. E-mail glenn_fishman{at}smtplink.mssm.edu

Abstract

Abstract—Manipulation of the mouse genome by traditional transgenic approaches has facilitated studies of gene function within the context of the intact organism and allowed for the creation of useful animal models of human disease. However, the timing of gene activation or repression is a critical determinant of phenotype, and the ability to regulate the temporal profile of transgene expression remains an important experimental goal. In this Mini Review, we describe the current status of systems to tightly regulate target gene expression in vivo, focusing on binary systems using chimeric transcription factors. Although experimental difficulties persist, regulated expression systems are beginning to produce conditional phenotypes with exciting experimental implications. We review the experience to date and examine the potential utility of these approaches within the context of cardiovascular medicine.

Key Words: mouse genome • gene expression • chimeric transcription • transgenic • conditional

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