title: beta-Arrestin1 knockout mice appear normal but demonstrate altered cardiac responses to beta-adrenergic stimulation.
abstract: beta-Arrestin1 knockout mice were studied to define the physiological role of beta-arrestin1 in the regulation of G protein-coupled receptors. beta-Arrestin1 is thought to be involved in the desensitization of many G protein-associated cell surface receptors, particularly beta-adrenergic receptors. Homozygous knockout mice are overtly normal. Resting cardiovascular parameters modulated by beta-adrenergic receptors such as heart rate, blood pressure, and left ventricular ejection fraction are not changed. However, homozygous mutants are more sensitive to beta-receptor agonist-stimulated increases in ejection fraction, consistent with a role of beta-arrestin1 in beta-adrenergic receptor desensitization. We conclude that beta-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, beta-arrestin1 does not appear to be required for development or for other essential biological functions.
authors.affiliation: Howard Hughes Medical Institute, Boston, Mass., USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Conner
authors.forename: M A
authors.initials: MA
authors.lastname: Mathier
authors.forename: R M
authors.initials: RM
authors.lastname: Mortensen
authors.forename: M
authors.initials: M
authors.lastname: Christe
authors.forename: S F
authors.initials: SF
authors.lastname: Vatner
authors.forename: C E
authors.initials: CE
authors.lastname: Seidman
authors.forename: J G
authors.initials: JG
authors.lastname: Seidman
mesh_terms: D000818:Animals; D019390:Arrestins / Q000235:genetics* / Q000502:physiology; D001794:Blood Pressure; D002874:Chromosome Mapping; D019204:GTP-Binding Proteins / Q000502:physiology; D018390:Gene Targeting; D006339:Heart Rate; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D011943:Receptors, Adrenergic, beta; D000071557:beta-Arrestins; D019204:GTP-Binding Proteins