Large-scale phenotyping efforts have demonstrated that approximately 25–30% of mouse gene knockouts cause intrauterine lethality. Analysis of these mutants has largely focused on the embryo and not the placenta, despite the crucial role of this extraembryonic organ for developmental progression. Here we screened 103 embryonic lethal and sub-viable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders program for placental phenotypes. We found that 68% of knockout lines that are lethal at or after mid-gestation exhibited placental dysmorphologies. Early lethality (embryonic days 9.5–14.5) is almost always associated with severe placental malformations. Placental defects correlate strongly with abnormal brain, heart and vascular development. Analysis of mutant trophoblast stem cells and conditional knockouts suggests that a considerable number of factors that cause embryonic lethality when ablated have primary gene function in trophoblast cells. Our data highlight the hugely under-appreciated importance of placental defects in contributing to abnormal embryo development and suggest key molecular nodes that govern placenta formation.

中文翻译：

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胎盘缺陷在胚胎致死小鼠突变体中非常普遍

大规模的表型研究表明，大约 25-30% 的小鼠基因敲除会导致宫内致死。对这些突变体的分析主要集中在胚胎而不是胎盘上，尽管这种胚胎外器官在发育进程中起着至关重要的作用。在这里，我们从胎盘表型破译发育障碍机制计划中筛选了 103 个胚胎致死和亚存活小鼠基因敲除系。我们发现 68% 在妊娠中期或之后致命的基因敲除系表现出胎盘畸形。早期致死率（胚胎期 9.5-14.5）几乎总是与严重的胎盘畸形有关。胎盘缺陷与异常的大脑、心脏和血管发育密切相关。对突变滋养层干细胞和条件性敲除的分析表明，大量消融时导致胚胎致死的因素在滋养层细胞中具有主要基因功能。我们的数据强调了胎盘缺陷在导致胚胎发育异常方面的重要性被大大低估，并提出了控制胎盘形成的关键分子节点。