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PMID:8917529
| Citation |
Jaber, M, Koch, WJ, Rockman, H, Smith, B, Bond, RA, Sulik, KK, Ross, J Jr, Lefkowitz, RJ, Caron, MG and Giros, B (1996) Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function. Proc. Natl. Acad. Sci. U.S.A. 93:12974-9 |
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| Abstract |
The beta-adrenergic receptor kinase 1 (beta ARK1) is a member of the G protein-coupled receptor kinase (GRK) family that mediates the agonist-dependent phosphorylation and desensitization of G protein-coupled receptors. We have cloned and disrupted the beta ARK1 gene in mice by homologous recombination. No homozygote beta ARK1-/- embryos survive beyond gestational day 15.5. Prior to gestational day 15.5, beta ARK1-/- embryos display pronounced hypoplasia of the ventricular myocardium essentially identical to the "thin myocardium syndrome" observed upon gene inactivation of several transcription factors (RXR alpha, N-myc, TEF-1, WT-1). Lethality in beta ARK1-/- embryos is likely due to heart failure as they exhibit a > 70% decrease in cardiac ejection fraction determined by direct in utero intravital microscopy. These results along with the virtual absence of endogenous GRK activity in beta ARK1-/- embryos demonstrate that beta ARK1 appears to be the predominant GRK in early embryogenesis and that it plays a fundamental role in cardiac development. |
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| Keywords |
Animals; Chimera; Cyclic AMP-Dependent Protein Kinases/biosynthesis; Cyclic AMP-Dependent Protein Kinases/genetics; Cyclic AMP-Dependent Protein Kinases/metabolism; DNA Primers; Embryonic and Fetal Development; Exons; Female; Fetal Death; Fetal Heart/physiology; Heart Defects, Congenital/embryology; Heart Defects, Congenital/genetics; Heart Defects, Congenital/pathology; Homozygote; Mice; Mice, Transgenic; Myocardium/enzymology; Polymerase Chain Reaction; Pregnancy; Recombination, Genetic; beta-Adrenergic Receptor Kinases |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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