Cooperative and antagonistic roles for Irx3 and Irx5 in cardiac morphogenesis and postnatal physiology

Analysis of the roles of Irx3 and Irx5 transcription factors in mouse heart development and postnatal heart function. Results show that show that Irx3 and Irx5 have redundant function in the in the endocardium to regulate atrioventricular canal morphogenesis and outflow tract formation. A postnatal deletion of Irx3 and Irx5 surprisingly results in a restoration of the repolarization gradient that is altered in Irx5 mutant hearts, suggesting a model whereby postnatal Irx3 activity is normally repressed by Irx5. 4 genotypes were analyzed: Irx5+/- (3 samples), Irx3-/-;Irx5+/- (4 samples), Irx5-/- (3 samples), Irx5-/-;Irx3-/- (4 samples). The Irx5+/- samples are the reference.本研究针对转录因子Irx3与Irx5在小鼠心脏发育及出生后心脏功能中的作用展开分析。结果显示，Irx3与Irx5在心内膜（endocardium）中存在功能冗余，可调控房室管形态发生与流出道形成。对Irx3与Irx5进行出生后敲除时，竟可恢复Irx5突变心脏中异常的复极化梯度，由此提出如下模型：正常生理状态下，出生后的Irx3活性会受到Irx5的抑制。本研究共分析4种基因型样本：Irx5+/-（3例）、Irx3-/-;Irx5+/-（4例）、Irx5-/-（3例）及Irx5-/-;Irx3-/-（4例），其中以Irx5+/-样本作为参照组。