β-Arrestin1 Knockout Mice Appear Normal but Demonstrate Altered Cardiac Responses to β-Adrenergic Stimulation

Abstract

Abstract β-Arrestin1 knockout mice were studied to define the physiological role of β-arrestin1 in the regulation of G protein–coupled receptors. β-Arrestin1 is thought to be involved in the desensitization of many G protein–associated cell surface receptors, particularly β-adrenergic receptors. Homozygous knockout mice are overtly normal. Resting cardiovascular parameters modulated by β-adrenergic receptors such as heart rate, blood pressure, and left ventricular ejection fraction are not changed. However, homozygous mutants are more sensitive to β-receptor agonist–stimulated increases in ejection fraction, consistent with a role of β-arrestin1 in β-adrenergic receptor desensitization. We conclude that β-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, β-arrestin1 does not appear to be required for development or for other essential biological functions.