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Loss of RBBP4 results in defective inner cell mass, severe apoptosis, hyperacetylated histones and preimplantation lethality in mice†.
Biology of Reproduction ( IF 3.6 ) Pub Date : 2020-04-14 , DOI: 10.1093/biolre/ioaa046
Xiaosu Miao 1 , Tieqi Sun 1 , Holly Barletta 1 , Jesse Mager 1 , Wei Cui 1, 2
Affiliation  

Retinoblastoma-binding protein 4 (RBBP4) (also known as chromatin-remodeling factor RBAP48) is an evolutionarily conserved protein that has been involved in various biological processes. Although a variety of functions have been attributed to RBBP4 in vitro, mammalian RBBP4 has not been studied in vivo. Here we report that RBBP4 is essential during early mouse embryo development. Although Rbbp4 mutant embryos exhibit normal morphology at E3.5 blastocyst stage, they cannot be recovered at E7.5 early post-gastrulation stage, suggesting an implantation failure. Outgrowth (OG) assays reveal that mutant blastocysts cannot hatch from the zona or can hatch but then arrest without further development. We find that while there is no change in proliferation or levels of reactive oxygen species, both apoptosis and histone acetylation are significantly increased in mutant blastocysts. Analysis of lineage specification reveals that while the trophoblast is properly specified, both epiblast and primitive endoderm lineages are compromised with severe reductions in cell number and/or specification. In summary, these findings demonstrate the essential role of RBBP4 during early mammalian embryogenesis.

中文翻译:

RBBP4 的缺失会导致小鼠内细胞团缺陷、严重的细胞凋亡、组蛋白过度乙酰化和植入前致死率†。

视网膜母细胞瘤结合蛋白 4 (RBBP4)(也称为染色质重塑因子 RBAP48)是一种进化上保守的蛋白质,参与了各种生物过程。尽管在体外RBBP4 具有多种功能,但尚未在体内研究哺乳动物 RBBP4 。在这里我们报告 RBBP4 在早期小鼠胚胎发育过程中是必不可少的。虽然Rbbp4突变胚胎在 E3.5 囊胚阶段表现出正常形态,在 E7.5 早期原肠胚形成阶段无法恢复,表明着床失败。生长 (OG) 分析表明突变囊胚不能从带状区孵化,或者可以孵化但随后停止而没有进一步发育。我们发现,虽然增殖或活性氧的水平没有变化,但突变体囊胚中的细胞凋亡和组蛋白乙酰化均显着增加。谱系规格分析表明,虽然滋养层被正确指定,但外胚层和原始内胚层谱系都因细胞数量和/或规格的严重减少而受到损害。总之,这些发现证明了 RBBP4 在早期哺乳动物胚胎发生过程中的重要作用。
更新日期:2020-04-14
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