Double homeobox genes are unique to eutherian mammals. It has been proposed that the DUXC clade of the double homeobox gene family, which is present in multicopy long tandem arrays, plays an essential role in zygotic genome activation (ZGA). We generated a deletion of the tandem array encoding the DUXC gene of mouse, Double homeobox (Dux), and found it surprisingly to be homozygous viable and fertile. We characterize the embryonic development and ZGA profile of knockout (KO) embryos, finding that zygotic genome activation still occurs, with only modest alterations in 2-cell embryo gene expression, no defect in in vivo preimplantation development, but an increased likelihood of post-implantation developmental failure, leading to correspondingly smaller litter sizes in the KO strain. While all known 2-cell specific Dux target genes are still expressed in the KO, a subset is expressed at lower levels. These include numerous genes involved in methylation, blastocyst development, and trophectoderm/placental development. We propose that rather than driving ZGA, which is a process common throughout the animal kingdom, DUXC genes facilitate a process unique to eutherian mammals, namely the post-implantation development enabled by an invasive placenta.

中文翻译：

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Dux 促进植入后发育，但对于合子基因组激活不是必需的

双同源盒基因是真兽类哺乳动物所独有的。已经提出，存在于多拷贝长串联阵列中的双同源盒基因家族的 DUXC 进化枝在合子基因组激活 (ZGA) 中起重要作用。我们删除了编码小鼠 DUXC 基因的串联阵列，Double homeobox (Dux)，并且令人惊讶地发现它是纯合的可行且可育的。我们对敲除 (KO) 胚胎的胚胎发育和 ZGA 谱进行了表征，发现合子基因组激活仍然发生，2 细胞胚胎基因表达只有适度的改变，体内植入前发育没有缺陷，但后-着床发育失败，导致 KO 菌株的窝产仔数相应变小。虽然所有已知的 2 细胞特异性 Dux 靶基因仍在 KO 中表达，但有一个子集以较低水平表达。这些包括许多参与甲基化、胚泡发育和滋养外胚层/胎盘发育的基因。我们建议，DUXC 基因不是驱动 ZGA，这是整个动物界常见的过程，而是促进了真兽类哺乳动物独有的过程，