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 cardiovascular physiology and pathology. A large number of gene knockout and overexpression models have been generated, including genes involved in blood pressure regulation, cardiac function and hemostasis. In this review we concentrate on two models, the endothelial NO synthase and the myoglobin knockout mice. It will be shown that the genetic approach of gene function analysis in mice not only provides new insight into the actual role of the encoded gene product, but also uncovers possible secondary alterations which compensate for the induced change. In the case of NOS knockout mice, upregulation of 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 function as shown by the elevated capillary density, which may enhance the oxygen supply to mitochondria. Thus, results obtained by the analysis of gene function in transgenic animals may differ from acute pharmacological interventions in that they reveal the striking ability of an intact organism to effectively adapt to chronic changes in gene expression.
Gödecke
A
A
Institut für Herz- und Kreislaufphysiologie, Heinrich Heine Universität, Düsseldorf, Germany. Axel.Goedecke@uni-duesseldorf.de
Schrader
J
J
D000222:Adaptation, Physiological; D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000502:physiology*; D009211:Myoglobin / Q000235:genetics*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
D009211:Myoglobin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse