© 1997 American Heart Association, Inc.
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ß-Arrestin1 Knockout Mice Appear Normal but Demonstrate Altered Cardiac Responses to ß-Adrenergic Stimulation
From the Howard Hughes Medical Institute and the Department of Genetics, Harvard Medical School, Boston, Mass (D.A.C., M.C., J.G.S.); the Department of Medicine, Allegheny General Hospital and the Allegheny University of the Health Sciences, Pittsburgh, Pa (M.A.M.); the Endocrine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (R.M.M.); the Allegheny University of the Health Sciences, Cardiovascular and Pulmonary Research Institute, Pittsburgh (S.F.V.); and the Brigham and Women's Hospital, Department of Medicine, and Howard Hughes Medical Institute, Boston (C.E.S.).
Correspondence to J.G. Seidman, Department of Genetics, Harvard Medical School, Alpert Building Room 533, 200 Longwood Ave, Boston, MA 02115. E-mail seidman{at}rascal.med.harvard.edu
Abstract ß-Arrestin1 knockout mice were studied to define the physiological role of ß-arrestin1 in the regulation of G protein–coupled receptors. ß-Arrestin1 is thought to be involved in the desensitization of many G protein–associated cell surface receptors, particularly ß-adrenergic receptors. Homozygous knockout mice are overtly normal. Resting cardiovascular parameters modulated by ß-adrenergic receptors such as heart rate, blood pressure, and left ventricular ejection fraction are not changed. However, homozygous mutants are more sensitive to ß-receptor agonist–stimulated increases in ejection fraction, consistent with a role of ß-arrestin1 in ß-adrenergic receptor desensitization. We conclude that ß-arrestin1 is important for in vivo G protein–coupled receptor desensitization and that this aspect of desensitization represents a mechanism for fine-tuning responses. However, ß-arrestin1 does not appear to be required for development or for other essential biological functions.
Key Words: ß-arrestin1 • knockout mice • desensitization • G protein–coupled receptor
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