Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function.
Data(s) |
12/11/1996
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Formato |
12974 - 12979 |
Identificador |
http://www.ncbi.nlm.nih.gov/pubmed/8917529 Proc Natl Acad Sci U S A, 1996, 93 (23), pp. 12974 - 12979 0027-8424 |
Relação |
Proc Natl Acad Sci U S A 10.1073/pnas.93.23.12974 |
Palavras-Chave | #Animals #Chimera #Cyclic AMP-Dependent Protein Kinases #DNA Primers #Embryonic and Fetal Development #Exons #Female #Fetal Death #Fetal Heart #Heart Defects, Congenital #Homozygote #Mice #Mice, Transgenic #Myocardium #Polymerase Chain Reaction #Pregnancy #Recombination, Genetic #beta-Adrenergic Receptor Kinases |
Tipo |
Journal Article |
Cobertura |
United States |
Resumo |
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. |
Idioma(s) |
ENG |