| The spectrum of cardiovascular anomalies in CHF1/Hey2 deficient mice reveals roles in endocardial cushion, myocardial and vascular maturation. | |
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MedLine Citation:
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PMID: 16242143 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CHF1/Hey2 null mice generated in different laboratories have discrepant cardiovascular phenotypes. To determine the effect of genetic background on phenotype, we backcrossed our knockout strain more than eight generations to the inbred strains BALB/c and C57BL/6. Knockout mice on these backgrounds showed disparate phenotypes. Mice on both backgrounds demonstrated ventricular septal defects (VSDs), tricuspid stenosis and mitral valve thickening, but at varying frequencies, suggesting a general defect in endocardial cushion remodeling. Additional defects seen exclusively on the C57BL/6 background included biventricular wall thinning and left ventricular enlargement, implying a more severe myocardial defect than previously observed. In addition, aortas and pulmonary arteries from these null mice had thinner walls. Intercrossing of the CHF1/Hey2 null mice on a C57BL/6 background with a C57BL/6 MLC2v-CHF1/Hey2 transgenic line overexpressing CHF1/Hey2 in the atrial and ventricular myocardium also rescued the VSD and myocardial phenotypes, but did not affect vascular wall thickness. Our results indicate that CHF1/Hey2 provides an important myocardial signal to the endocardial cushion for proper septation and valve formation and also plays an important role in maturation of the myocardium and vasculature. |
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Authors:
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Yasuhiko Sakata; Nobutaka Koibuchi; Fan Xiang; Joey M Youngblood; Caramai N Kamei; Michael T Chin |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2005-10-19 |
Journal Detail:
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Title: Journal of molecular and cellular cardiology Volume: 40 ISSN: 0022-2828 ISO Abbreviation: J. Mol. Cell. Cardiol. Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-01-31 Completed Date: 2008-02-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0262322 Medline TA: J Mol Cell Cardiol Country: England |
Other Details:
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Languages: eng Pagination: 267-73 Citation Subset: IM |
Affiliation:
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Vascular Medicine Research, Brigham and Women's Hospital and Harvard Medical School, 65 Landsdowne Street, Room 277, Cambridge, MA 02139, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aorta / abnormalities Basic Helix-Loop-Helix Transcription Factors / deficiency*, genetics Cardiovascular Abnormalities / genetics* Endocardial Cushion Defects / genetics Epigenesis, Genetic* Gene Deletion Heart / growth & development Heart Ventricles / abnormalities Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mitral Valve / abnormalities Mutation Myocardium / metabolism Phenotype Repressor Proteins / genetics Tricuspid Valve Stenosis / genetics Tunica Media / abnormalities |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL 67141-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Basic Helix-Loop-Helix Transcription Factors; 0/Hey2 protein, mouse; 0/Repressor Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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