Firulli A B, McFadden D G, Lin Q, Srivastava D, Olson E N
Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, 75235-9148, USA.
Nat Genet. 1998 Mar;18(3):266-70. doi: 10.1038/ng0398-266.
The basic helix-loop-helix (bHLH) transcription factors, Hand1 and Hand2 (refs 1,2), also called eHand/Hxt/Thing1 and dHand/Hed/Thing2 (refs 3,4), respectively, are expressed in the heart and certain neural-crest derivatives during embryogenesis. In addition, Hand1 is expressed in extraembryonic membranes, whereas Hand2 is expressed in the deciduum. Previous studies have demonstrated that Hand2 is required for formation of the right ventricle of the heart and the aortic arch arteries. We have generated a germline mutation in the mouse Hand1 gene by replacing the first coding exon with a beta-galactosidase reporter gene. Embryos homozygous for the Hand1 null allele died between embryonic days 8.5 and 9.5 and exhibited yolk sac abnormalities due to a deficiency in extraembryonic mesoderm. Heart development was also perturbed and did not progress beyond the cardiac-looping stage. Our results demonstrate important roles for Hand1 in extraembryonic mesodermal and heart development.
基本螺旋-环-螺旋（bHLH）转录因子Hand1和Hand2（参考文献1、2），也分别称为eHand/Hxt/Thing1和dHand/Hed/Thing2（参考文献3、4），在胚胎发育过程中表达于心脏和某些神经嵴衍生物中。此外，Hand1在胚外膜中表达，而Hand2在蜕膜中表达。先前的研究表明，心脏右心室和主动脉弓动脉的形成需要Hand2。我们通过用β-半乳糖苷酶报告基因替换第一个编码外显子，在小鼠Hand1基因中产生了种系突变。Hand1无效等位基因的纯合胚胎在胚胎第8.5天至9.5天之间死亡，并由于胚外中胚层缺陷而表现出卵黄囊异常。心脏发育也受到干扰，未超过心脏环化阶段。我们的结果表明Hand1在胚外中胚层和心脏发育中起重要作用。
