Murata Kenji, Degmetich Sean, Kinoshita Masato, Shimada Eriko
Department of Animal Science, University of California, Davis, CA 95616, USA.
Dev Growth Differ. 2009 Feb;51(2):95-107. doi: 10.1111/j.1440-169X.2008.01084.x.
The congenital heart disease 5 (CHD5)/tryptophan rich basic protein (WRB) is a protein containing a tryptophan-rich carboxy-terminal region, which was discovered in the human fetal heart. In humans, this CHD5/WRB is located between the markers ACTL5-D21S268 within the Down syndrome (DS) Region-2 at chromosome 21. Congenital heart disease is commonly linked to DS patients. The functions of this gene product are unknown. To identify the functions of CHD5/WRB in heart formation during embryogenesis, the medaka CHD5 cDNA (mCHD5) was isolated and its gene expression pattern and the localization of its gene product were investigated. The obtained mCHD5 belongs to the CHD5 superfamily, whose members include coiled-coil proteins. The mCHD5 gene was found to be expressed in the developing heart after stage 28 at which the chamber (ventricle and atrium) differentiation in the heart tube is initiated in the embryo. Its gene product was also detected in the developing heart at embryonic stage 28 and 35. Knocking-down of mCHD5 function caused severe cardiac disorder, including abnormal chamber differentiation, abnormal looping and ocular abnormality such as Cyclops. Our results provide the mCHD5 gene expression pattern as well as its physiological role during heart formation in a vertebrate model system.
先天性心脏病5（CHD5）/富含色氨酸的碱性蛋白（WRB）是一种在人类胎儿心脏中发现的、含有富含色氨酸的羧基末端区域的蛋白质。在人类中，这种CHD5/WRB位于21号染色体上唐氏综合征（DS）区域2内的ACTL5 - D21S268标记之间。先天性心脏病通常与唐氏综合征患者有关。该基因产物的功能尚不清楚。为了确定CHD5/WRB在胚胎发育过程中心脏形成中的功能，分离了青鳉CHD5 cDNA（mCHD5），并研究了其基因表达模式及其基因产物的定位。所获得的mCHD5属于CHD5超家族，其成员包括卷曲螺旋蛋白。发现mCHD5基因在胚胎发育到第28阶段后在发育中的心脏中表达，此时心脏管中的腔室（心室和心房）分化在胚胎中开始。在胚胎发育的第28和35阶段，在发育中的心脏中也检测到了其基因产物。敲低mCHD5的功能会导致严重的心脏紊乱，包括腔室分化异常、环化异常以及独眼等眼部异常。我们的结果提供了mCHD5基因在脊椎动物模型系统心脏形成过程中的表达模式及其生理作用。
