An In Vivo Map of Bone Morphogenetic Protein 2 Post-Transcriptional Repression in the Heart
An In Vivo Map of Bone Morphogenetic Protein 2 Post-Transcriptional Repression in the Heart
复制标题
DOI：
10.1002/dvg.20757
复制
发表时间：
2011-11-01
期刊：
影响因子：
1.5
通讯作者：
Rogers, Melissa B.
中科院分区：
文献类型：
--
作者：
Kruithof, Boudewijn P. T.;Xu, Junwang;Rogers, Melissa B.
Bmp2 3'非翻译区 (UTR) 序列具有在哺乳动物和鱼类之间保守的序列，可以在转录后激活或抑制蛋白质合成。我们开发了小鼠胚胎细胞图谱，其中该有效的 Bmp2 调节序列通过使用 lacZ 报告基因转基因发挥作用，该基因的 3'UTR 带有位于超保守序列两侧的两个 loxP 位点。 Cre重组酶介导的超保守序列缺失导致心外膜、心外膜和心外膜衍生细胞（EPDC）以及具有已知心外膜贡献的组织（冠状血管和瓣膜）中强烈异位表达。心外膜/间皮细胞 (EMC) 系中报告基因的瞬时转染证实了这种抑制。重组转基因的异位表达也发生在主动脉、出口隔膜、后心丛、心脏和心外神经以及神经节中。 Bmp2 在发育中的心脏中受到动态调节。 3'UTR 介导的抑制 BMP2 合成的机制可能与先天性心脏和脉管系统畸形以及涉及 BMP2 合成异常的成人疾病有关。创世纪 49:841-850, 2011。(C) 2011 Wiley periodicals, Inc.
The Bmp2 3'untranslated region (UTR) sequence bears a sequence conserved between mammals and fishes that can post-transcriptionally activate or repress protein synthesis. We developed a map of embryonic cells in the mouse where this potent Bmp2 regulatory sequence functions by using a lacZ reporter transgene with a 3'UTR bearing two loxP sites flanking the ultra-conserved sequence. Cre-recombinase-mediated deletion of the ultra-conserved sequence caused strong ectopic expression in proepicardium, epicardium and epicardium-derived cells (EPDC) and in tissues with known epicardial contributions (coronary vessels and valves). Transient transfections of reporters in the epicardial/mesothelial cell (EMC) line confirmed this repression. Ectopic expression of the recombined transgene also occurred in the aorta, outlet septum, posterior cardiac plexus, cardiac and extracardiac nerves and neural ganglia. Bmp2 is dynamically regulated in the developing heart. 3'UTR-mediated mechanisms that restrain BMP2 synthesis may be relevant to congenital heart and vasculature malformations and to adult diseases involving aberrant BMP2 synthesis. genesis 49:841-850, 2011. (C) 2011 Wiley Periodicals, Inc.