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Early Embryonic Lethality of Mice Lacking the Essential Protein SNEV

机译:缺乏必需蛋白SNEV的小鼠的早期胚胎致死率

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SNEV (Prp19, Pso4, NMP200) is a nuclear matrix protein known to be involved in pre-mRNA splicing, ubiquitylation, and DNA repair. In human umbilical vein endothelial cells, SNEV overexpression delayed the onset of replicative senescence. Here we analyzed the function of the mouse SNEV gene in vivo by employing homologous recombination in mice and conclude that SNEV is indispensable for early mouse development. Mutant preimplantation embryos initiated blastocyst formation but died shortly thereafter. Outgrowth of SNEV-null blastocysts showed a lack of proliferation of cells of the inner cell mass, which subsequently underwent cell death. While SNEV-heterozygous mice showed no overt phenotype, heterozygous mouse embryonic fibroblast cell lines with reduced SNEV levels displayed a decreased proliferative potential in vitro. Our experiments demonstrate that the SNEV protein is essential, functionally nonredundant, and indispensable for mouse development.
机译:SNEV(Prp19,Pso4,NMP200)是一种核基质蛋白,已知参与mRNA的前期剪接,泛素化和DNA修复。在人脐静脉内皮细胞中,SNEV的过表达延迟了复制性衰老的发作。在这里,我们通过在小鼠中使用同源重组分析了小鼠 EM 基因在体内的功能,并得出结论,SNEV对于早期小鼠发育是必不可少的。突变的植入前胚胎开始胚泡形成,但此后不久死亡。 SNEV -无效的胚泡的生长表明缺乏内部细胞团的细胞增殖,随后细胞死亡。虽然 SNEV -杂合子小鼠没有明显的表型,但是具有降低的SNEV水平的杂合子小鼠胚胎成纤维细胞系在体外显示出降低的增殖潜能。我们的实验证明SNEV蛋白是必需的,功能上非冗余的,并且对于小鼠发育是必不可少的。

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