Adaptive mechanisms of the cardiovascular system in transgenic - mice lessons from eNOS and myoglobin knockout mice

Transgenic mice have turned out to be important in the analysis of cardiova scular physiology and pathology. A large number of gene knockout and overex pression models have been generated, including genes involved in blood pres sure regulation, cardiac function and hemostasis. In this review we concent rate on two models,the endothelial NO synthase and the myoglobin knockout m ice. It will be shown that the genetic approach of gene function analysis i n mice not only provides new insight into the actual role of the encoded ge ne product, but also uncovers possible secondary alterations which compensa te for the induced change. In the case of NOS knockout mice, upregulation o f other NOS isoforms, induction of signal molecules such as prostaglandins or endothelium-derived hyperpolarizing factor may conserve the vasodilatory potential of NOS deficient vessels. In the case of myoglobin knockout mice , even structural changes may contribute to compensate a loss of gene funct ion as shown by the elevated capillary density, which may enhance the oxyge n supply to mitochondria. Thus, results obtained by the analysis of gene fu nction in transgenic animals may differ from acute pharmacological interven tions in that they reveal the striking ability of an intact organism to eff ectively adapt to chronic changes in gene expression.