Regulated expression of foreign genes in the rodent heart

Animal models provide enormous utility for deciphering complex interactions on an organismal level. One of the most powerful approaches toward influencing the behavior of an animal is by altering its complement of genetic information. In combination with improving techniques to manipulate the mammalian genome, it is note possible to create defined genetic alterations and examine the resulting phenotype in the genetically modified animal. These novel models have been. especially useful for defining the role of candidate genes during the normal program of development and identifying disturbances in gene function, which are associated with various pathologic states. Alterations in the genetic makeup of mammals have primarily been carried out in the mouse, resulting in, either gain-of-function or loss-of-function mutants. Although changes in gene expression resulting from modification of the mouse genome can be targeted to specific cell lineages, such as the cardiac myocyte, a satisfactory mechanism has not existed for temporally regulating these processes in vivo. We recently developed a system to tightly and reversibly control transgene expression in the hearts of mice. This article describes this strategy and discuss potential applications of this novel approach for studies of cardiac development and function.