The Role of Sorting Nexin 17 in Cardiac Development

Homozygous deletion of the SNX17 gene in rats resulted in mid-gestational embryonic lethality which was accompanied by congenital heart defects, including in the double-outlet right ventricle, atrioventricular and ventricular septal defects. To elucidate the potential mechanisms underlying development of cardiac OFT defects induced by SNX17 knockout, we performed RNA-seq analysis in cardiac outflow tract (OFT) tissues isolated from WT and HO embryos at E13.5. A total of 262 differentially expressed genes (DEGs) were identified between WT and HO samples, of which 94 and 168 were up-regulated and down-regulated, respectively. Analysis of biological functions of the DEGs, via Gene Ontology (GO), revealed that the up-regulated genes were mainly involved in heart development, and negative regulation of the intrinsic apoptotic pathway, while the down-regulated DEGs were associated with cell adhesion, extracellular organization, and negative regulation of the Wnt signaling pathway.大鼠分选连接蛋白17（SNX17）基因的纯合缺失可导致妊娠中期胚胎致死，并伴随先天性心脏缺陷，包括右心室双出口、房室间隔缺损与室间隔缺损。为阐明SNX17敲除诱导心脏流出道（cardiac outflow tract, OFT）缺陷发生的潜在分子机制，本研究对胚胎第13.5天（E13.5）野生型（WT）与纯合敲除（HO）胚胎的心脏流出道组织进行了RNA测序（RNA-seq）分析。最终在WT与HO样本间共鉴定得到262个差异表达基因（DEGs），其中94个基因表达上调，168个基因表达下调。通过基因本体（Gene Ontology, GO）对上述差异表达基因开展生物学功能富集分析后发现，上调基因主要参与心脏发育及内源性凋亡通路的负调控过程，而下调基因则与细胞黏附、细胞外结构组织及Wnt信号通路的负调控密切相关。