Ventricular septal defect and cardiomyopathy in mice lacking the transcription factor CHF1/Hey2
Ventricular septal defect and cardiomyopathy in mice lacking the transcription factor CHF1/Hey2
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DOI：
10.1073/pnas.252648999
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发表时间：
2002-12-10
影响因子：
11.1
通讯作者：
Chin, MT
中科院分区：
文献类型：
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作者：
Sakata, Y;Kamei, CN;Chin, MT
室间隔缺损在人类婴儿中很常见，但控制室间隔的遗传程序知之甚少。在这里，我们报告说，有针对性的破坏心血管基础螺旋-环-螺旋因子（CHF）1/Hey 2基因的小鼠表现出孤立的室间隔缺损。这些缺陷主要导致无法茁壮成长。小鼠通常在出生后的前3周内死亡，并表现出肺和肝充血。这种表型的突变率因遗传背景而异，表明存在修饰基因。其他心脏特异性基因的表达模式不受影响。在少数存活到成年的混合遗传背景的动物中，大多数发展为心肌病，但没有室间隔缺损。我们的研究结果表明，CHF 1起着重要的作用，在哺乳动物心脏发育的心室间隔的调节，是重要的正常心肌收缩力。这些小鼠为研究室间隔缺损和心肌病的个体发育和自然史提供了有用的模型。
Ventricular septal defects are common in human infants, but the genetic programs that control ventricular septation are poorly understood. Here we report that mice with a targeted disruption of the cardiovascular basic helix-loop-helix factor (CHF)1/Hey2 gene show isolated ventricular septal defects. These defects result primarily in failure to thrive. Mice often succumbed within the first 3 wk after birth and showed pulmonary and liver congestion. The penetrance of this phenotype varied, depending on genetic background, suggesting the presence of modifier genes. Expression patterns of other cardiac-specific genes were not affected. Of the few animals on a mixed genetic background that survived to adulthood, most developed a cardiomyopathy but did not have ventricular septal defects. Our results indicate that CHF1 plays an important role in regulation of ventricular septation in mammalian heart development and is important for normal myocardial contractility. These mice provide a useful model for the study of the ontogeny and natural history of ventricular septal defects and cardiomyopathy.