Many aspects of the functional role of the E3 ubiquitin ligase Hectd1 in embryogenesis and in cell biology still remain to be elucidated. In order to contribute to this task we now report the generation of a new transgenic mouse model for Hectd1 using the gene trap strategy. The HECT domain deletion mutant mouse was created by inserting a β-geo cassette into the Hectd1 locus. Mice homozygous for Hectd1-mutant showed early embryonic lethality with abnormal placental development and defective of neural tube closure resulting in exencephaly. The thickness of the placenta of both Hectd1-mutant homozygous and heterozygous mice was distinctly thinner than that of wildtype mice, the difference being most pronounced in the labyrinth layer of the placenta. We also addressed the temporal and spatial expression profiles of Hectd1 in adult tissues by X-gal staining. Hectd1 expression was detected in specific cell populations of most but not all tissues of the adult organism. Furthermore, the expression of Hectd1 was regulated by insulin and by both heat and hypoxia. Thus, our studies reveal that Hectd1 is indispensable for normal embryogenesis and fetal survival. The generation of this new Hectd1 mutant mouse model provides ample opportunities to study the function of Hectd1 in mammalian cells in detail.

E3泛素连接酶Hectd1在胚胎发生和细胞生物学中的功能性作用的许多方面仍有待阐明。为了对此任务做出贡献，我们现在报告使用基因捕获策略为Hectd1生成新的转基因小鼠模型。通过将β-geo盒插入Hectd1基因座来创建HECT域缺失突变小鼠。Hectd1突变体纯合子的小鼠表现出早期胚胎致死性，胎盘发育异常，神经管闭合缺陷，导致运动过度。两者的胎盘厚度Hectd1突变纯合子和杂合子小鼠明显比野生型小鼠瘦，差异在胎盘的迷宫层最明显。我们还通过X-gal染色处理了Hectd1在成人组织中的时空表达谱。在成年生物的大多数但不是所有组织的特定细胞群中检测到Hectd1表达。此外，Hectd1的表达受胰岛素以及受热和缺氧的调节。因此，我们的研究表明，Hectd1对于正常的胚胎发生和胎儿存活是必不可少的。这种新的Hectd1突变小鼠模型的产生提供了充分的机会来详细研究Hectd1在哺乳动物细胞中的功能。