beta-Arrestin1 knockout mice appear normal but demonstrate altered cardiac responses to beta-adrenergic stimulation.
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.
Conner
D A
DA
Howard Hughes Medical Institute, Boston, Mass., USA.
Mathier
M A
MA
Mortensen
R M
RM
Christe
M
M
Vatner
S F
SF
Seidman
C E
CE
Seidman
J G
JG
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
D019390:Arrestins; D011943:Receptors, Adrenergic, beta; D000071557:beta-Arrestins; D019204:GTP-Binding Proteins