Jiao Kai, Kulessa Holger, Tompkins Kevin, Zhou Yingna, Batts Lorene, Baldwin H Scott, Hogan Brigid L M
Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Genes Dev. 2003 Oct 1;17(19):2362-7. doi: 10.1101/gad.1124803. Epub 2003 Sep 15.
Proper septation and valvulogenesis during cardiogenesis depend on interactions between the myocardium and the endocardium. By combining use of a hypomorphic Bone morphogenetic protein 4 (Bmp4) allele with conditional gene inactivation, we here identify Bmp4 as a signal from the myocardium directly mediating atrioventricular septation. Defects in this process cause one of the most common human congenital heart abnormalities, atrioventricular canal defect (AVCD). The spectrum of defects obtained through altering Bmp4 expression in the myocardium recapitulates the range of AVCDs diagnosed in patients, thus providing a useful genetic model with AVCD as the primary defect.
心脏发生过程中正确的分隔和瓣膜形成依赖于心肌层和心内膜之间的相互作用。通过将低活性骨形态发生蛋白4（Bmp4）等位基因与条件性基因失活相结合，我们在此确定Bmp4是一种来自心肌层的信号，直接介导房室分隔。这一过程中的缺陷会导致人类最常见的先天性心脏异常之一，即房室管缺损（AVCD）。通过改变心肌层中Bmp4表达所获得的缺陷谱概括了在患者中诊断出的AVCD范围，从而提供了一个以AVCD为主要缺陷的有用遗传模型。
