Gi. Fishman, TIMING IS EVERYTHING IN LIFE - CONDITIONAL TRANSGENE EXPRESSION IN THE CARDIOVASCULAR-SYSTEM, Circulation research, 82(8), 1998, pp. 837-844
Manipulation of the mouse genome by traditional transgenic approaches
has facilitated studies of gene function within the context of the int
act organism and allowed for the creation of useful animal models of h
uman disease. However, the timing of gene activation or repression is
a critical determinant of phenotype, and the ability to regulate the t
emporal profile of transgene expression remains an important experimen
tal goal. In this Mini Review, we describe the current status of syste
ms to tightly regulate target gene expression in vivo, focusing on bin
ary systems using chimeric transcription factors. Although experimenta
l 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 o
f these approaches within the context of cardiovascular medicine.