The molecular mechanisms regulating sympathetic innervation of the heart during embryogenesis and its importance for cardiac development and function remain to be fully elucidated. We generated mice in which conditional knockout (CKO) of the Hif1a gene encoding the transcription factor hypoxia-inducible factor 1α (HIF-1α) is mediated by an Islet1-Cre transgene expressed in the cardiac outflow tract, right ventricle and atrium, pharyngeal mesoderm, peripheral neurons, and hindlimbs. These Hif1aCKO mice demonstrate significantly decreased perinatal survival and impaired left ventricular function. The absence of HIF-1α impaired the survival and proliferation of preganglionic and postganglionic neurons of the sympathetic system, respectively. These defects resulted in hypoplasia of the sympathetic ganglion chain and decreased sympathetic innervation of the Hif1aCKO heart, which was associated with decreased cardiac contractility. The number of chromaffin cells in the adrenal medulla was also decreased, indicating a broad dependence on HIF-1α for development of the sympathetic nervous system.

• Klíčová slova
• cardiac innervation, coronary artery branching, hypoxia, sympathetic neurons, tyrosine hydroxylase,
• MeSH
• anomálie koronárních cév embryologie   MeSH
• chromafinní buňky MeSH
• dřeň nadledvin embryologie   inervace   MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa fyziologie   MeSH
• koronární cévy embryologie   MeSH
• myši knockoutované MeSH
• myši transgenní MeSH
• myši MeSH
• srdce embryologie   inervace   MeSH
• sympatická ganglia embryologie   růst a vývoj   MeSH
• sympatický nervový systém enzymologie   růst a vývoj   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
• Hif1a protein, mouse MeSH Prohlížeč