Lu Shun Yan, Sheikh Farah, Sheppard Patricia C, Fresnoza Agnes, Duckworth Mary Lynn, Detillieux Karen A, Cattini Peter A
Department of Physiology, University of Manitoba, 730 William Avenue, Winnipeg, MB R3E3J7, Canada.
Biochem Biophys Res Commun. 2008 Aug 22;373(2):270-4. doi: 10.1016/j.bbrc.2008.06.029. Epub 2008 Jun 17.
Fibroblast growth factor 16 (FGF-16) expression has previously been detected in mouse heart at mid-gestation in the endocardium and epicardium, suggesting a role in embryonic heart development. More specifically, exogenously applied FGF-16 has been shown to stimulate growth of embryonic myocardial cells in tissue explants. We have generated mice lacking FGF-16 by targeting the Fgf16 locus on the X chromosome. Elimination of Fgf16 expression resulted in embryonic death as early as day 11.5 (E11.5). External abnormalities, including hemorrhage in the heart and ventral body region as well as facial defects, began to appear in null embryos from E11.5. Morphological analysis of FGF-16 null hearts revealed cardiac defects including chamber dilation, thinning of the atrial and ventricular walls, and poor trabeculation, which were visible at E10.5 and more pronounced at E11.5. These findings indicate FGF-16 is required for embryonic heart development in mid-gestation through its positive effect on myocardial growth.
先前已在妊娠中期小鼠心脏的心内膜和心外膜中检测到成纤维细胞生长因子16(FGF - 16)的表达,这表明其在胚胎心脏发育中发挥作用。更具体地说,已证明外源性应用FGF - 16可刺激组织外植体中胚胎心肌细胞的生长。我们通过靶向X染色体上的Fgf16基因座生成了缺乏FGF - 16的小鼠。Fgf16表达的消除早在第11.5天(E11.5)就导致胚胎死亡。从E11.5开始,在缺失FGF - 16的胚胎中开始出现外部异常,包括心脏和腹侧身体区域出血以及面部缺陷。对FGF - 16缺失心脏的形态学分析显示出心脏缺陷,包括心室扩张、心房和心室壁变薄以及小梁形成不良,这些在E10.5时可见,在E11.5时更为明显。这些发现表明,FGF - 16通过其对心肌生长的积极作用,在妊娠中期的胚胎心脏发育中是必需的。