© 1996 American Heart Association, Inc.
Articles |
Transgenic Manipulation of Myocardial G Protein–Coupled Receptors and Receptor Kinases
From the Departments of Surgery (W.J.K., C.A.M.) and Medicine and Biochemistry (R.J.L.) and the Howard Hughes Medical Institute (R.J.L.), Duke University Medical Center, Durham, NC.
Correspondence to Robert J. Lefkowitz, MD, Howard Hughes Medical Institute, Duke University Medical Center, DUMC Box 3821, Durham, NC 27710.
Key Words: transgenic mice • G protein–coupled receptor • G protein–coupled receptor kinase • ß-adrenergic receptor kinase
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Introduction |
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The ability to maintain and manipulate mouse embryos in vitro, perfected over the last decade, has launched the expanding field of transgenic experimentation. With the successful insertion of foreign genes into the mouse genome, important transgenic models have emerged in several venues of biomedical research. Transgenic mice permit investigation of the consequences of a protein's overexpression in a particular tissue. In addition, the loss of function of a protein or enzyme can be examined by tissue-targeted overexpression of an inhibitor peptide or a dominant-negative mutant. Elimination of a protein from all tissues can also be achieved by "knockout" technology, where a gene is disrupted by homologous recombination. These approaches are well suited to study the physiological roles of cellular proteins.
Transgenic models geared toward the study of cardiovascular regulation have recently been described and provide powerful tools to study normal and compromised cardiac physiology. Some of these transgenic models address changes in blood pressure and apolipoprotein levels as well as the consequences of overexpression of specific nuclear factors.1 Most recently, transgenic mice have been developed in which sarcolemmal G protein–coupled receptor signaling has been altered; these animals provide new information regarding the role of signal transduction in cardiac function. Manipulation of various components of the myocardial AR system has led to novel agonist-independent approaches to enhance signaling and augment cardiac function. This mini review summarizes these recent transgenic studies, which have provided unique experimental models for the study of receptor signaling in both normal and diseased myocardium.
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Myocardial ARs |
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Probably the most
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