期刊
DEVELOPMENTAL BIOLOGY
卷 358, 期 2, 页码 368-378出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2011.07.037
关键词
Congenital heart disease; Transcription factors; Heart development; Double outlet right ventricle; Endocardial cushion; Septal defects
资金
- Canadian Institutes of Health Research
Members of the GATA family of transcription factors are critical regulators of heart development and mutations in 2 of them. GATA4 and GATA6 are associated with outflow tract and septal defects in human. The heart expresses 3 GATA factors, GATA4, 5 and 6 in a partially overlapping pattern. Here, we report that compound Gata4/Gata5 and Gata5/Gata6 mutants die embryonically or perinatally due to severe congenital heart defects. Almost all Gata4(+/-)Gata5(+/-) mutant embryos have double outlet right ventricles (DORV), large ventricular septal defects (VSD) as well as hypertrophied mitral and tricuspid valves. Only 25% of double compound Gata4/Gata5 heterozygotes survive to adulthood and these mice have aortic stenosis. Compound loss of a Gata5 and a Gata6 allele also leads to DORVs associated with subaortic VSDs. Expression of several transcription factors important for endocardial and myocardial cell differentiation, such as Tbx20, Mef2c, Hey1 and Hand2, was reduced in compound heterozygote embryos. These findings suggest the existence of important genetic interactions between Gata5 and the 2 other cardiac GATA factors in endocardial cushion formation and outflow tract morphogenesis. The data identify GATA5 as a potential genetic modifier of congenital heart disease and provide insight for elucidating the genetic basis of an important class of human birth defects. (C) 2011 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据