D'Alonzo Donato, Emch Fabienne Hélène, Shen Xiaoli, Bruder Elisabeth, De Geyter Christian, Zhang Hong
Department of Biomedicine, University Hospital, University of Basel, Hebelstrasse 20, CH-4031, Basel, Switzerland.
Clinic of Gynecological Endocrinology and Reproductive Medicine, University Hospital, University of Basel, Spitalstrasse 21, CH-4031, Basel, Switzerland.
Gene Expr Patterns. 2019 Dec;34:119064. doi: 10.1016/j.gep.2019.119064. Epub 2019 Jul 10.
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在胚胎发育和细胞生物学中的功能作用的许多方面仍有待阐明。为了推动这项工作，我们现在报告利用基因捕获策略生成一种新的Hectd1转基因小鼠模型。通过将β-geo盒插入Hectd1基因座来创建HECT结构域缺失突变小鼠。Hectd1突变纯合子小鼠表现出早期胚胎致死性，伴有胎盘发育异常和神经管闭合缺陷，导致无脑畸形。Hectd1突变纯合子和杂合子小鼠的胎盘厚度明显薄于野生型小鼠，这种差异在胎盘的迷路层最为明显。我们还通过X-gal染色研究了Hectd1在成年组织中的时空表达谱。在成年生物体的大多数但并非所有组织的特定细胞群体中检测到了Hectd1的表达。此外，Hectd1的表达受胰岛素以及热和缺氧的调节。因此，我们的研究表明Hectd1对于正常胚胎发育和胎儿存活是不可或缺的。这种新的Hectd1突变小鼠模型的产生为详细研究Hectd1在哺乳动物细胞中的功能提供了充足的机会。
