Numb和numblike基因对小鼠胚胎期心血管发育的影响

Effect of Numb and Numblike on Cardiovascular Development of Mouse Embryo

Numb是近年来发现的第一个在多细胞生物中决定细胞命运的信号分子。在哺乳动物中,有4种不同的剪接形式,和同源分子numblike一起构成5种不同的分子。我们用血管内皮细胞特异性重组酶Tie2-cre同时介导敲除numb和numblike,发现小鼠在胚胎期E10.0出现表型,体积变小,E10.5出现心包积液(pericardial effusion)的病理模型,背主动脉管径显著变细,心脏小梁柱显著减少,E11.0前死亡。这些结果说明numb和numblike在心血管发育中有重要作用。本实验对研究心血管发育的分子细胞机制有重要指导意义,并将加深对心血管疾病发生新的认识。

Numb is the first signaling molecule found to determine cell fate in multi-cellular organisms. In mammalian, numb has four different splice variants, with a homology molecule numblike. We utilized endothelial specific recombinase Tie2-cre to knockout numb and numblike in endothelium and endocardium, and we found that the mutant mice were smaller in size at E10.0, with pericardial effusion at E10.5; besides, the dorsa aorta became thinner, and the mutant had notable defective trabeculation, but lethal beyond E11.0. These results suggest that numb and numblike play an important role in cardiovascular development, which would help us to search the molecular mechanism of cardiovascular development, as well as to study the genesis of angiocardiopathy.