Endonuclease G is required for early embryogenesis and normal apoptosis in mice
Endonuclease G is required for early embryogenesis and normal apoptosis in mice
复制标题
DOI：
10.1073/pnas.2636393100
复制
发表时间：
2003-12
影响因子：
11.1
通讯作者：
Jianhua Zhang;Mei Dong;Lily Y. Li;Yunxia Fan;Purnima Pathre;J. Dong;D. Lou;J. Wells;Danyvid Olivares-Villagómez;L. Van Kaer;Xiaodong Wang;Ming Xu
中科院分区：
文献类型：
--
作者：
Jianhua Zhang;Mei Dong;Lily Y. Li;Yunxia Fan;Purnima Pathre;J. Dong;D. Lou;J. Wells;Danyvid Olivares-Villagómez;L. Van Kaer;Xiaodong Wang;Ming Xu
核酸内切酶G（EndoG）是一种核编码的线粒体蛋白，据报道对于细胞凋亡期间的核DNA片段化和线粒体DNA复制都是重要的。为了评估EndoG的体内功能，我们研究了EndoG缺乏对细胞和小鼠的影响。我们发现EndoG纯合突变胚胎在胚胎第2.5天至第3.5天之间死亡。来自EndoG杂合突变体和野生型小鼠的排卵卵母细胞中的线粒体DNA拷贝数相似，表明EndoG参与与线粒体DNA复制无关的细胞功能。有趣的是，我们发现来自EndoG杂合突变小鼠的细胞对肿瘤坏死因子α和星形孢菌素诱导的细胞死亡表现出增加的抗性。此外，与野生型小鼠相比，EndoG杂合突变小鼠精原细胞的自发性细胞死亡显著减少。与野生型细胞相比，EndoG+/-胸腺细胞和脾细胞中的DNA片段化也减少，以及与野生型小鼠相比，体内EndoG+/-胸腺中的DNA片段化也减少。这些发现表明，EndoG在早期胚胎发生过程中是必不可少的，并在正常的细胞凋亡和核DNA片段化中起着关键作用。
Endonuclease G (EndoG) is a nuclear-encoded mitochondrial protein reported to be important for both nuclear DNA fragmentation during apoptosis and mitochondrial DNA replication. To evaluate the in vivo function of EndoG, we have investigated the effects of EndoG deficiency in cells and mice. We found that EndoG homozygous mutant embryos die between embryonic days 2.5 and 3.5. Mitochondrial DNA copy numbers in ovulated oocytes from EndoG heterozygous mutant and wild-type mice are similar, suggesting that EndoG is involved in a cellular function unrelated to mitochondrial DNA replication. Interestingly, we found that cells from EndoG heterozygous mutant mice exhibit increased resistance to both tumor necrosis factor α- and staurosporine-induced cell death. Moreover, spontaneous cell death of spermatogonia in EndoG heterozygous mutant mice is significantly reduced compared with wild-type mice. DNA fragmentation is also reduced in EndoG+/- thymocytes and splenocytes compared with wild-type cells, as well as in EndoG+/- thymus in vivo compared with that of the wild-type mice, on activation of apoptosis. These findings indicate that EndoG is essential during early embryogenesis and plays a critical role in normal apoptosis and nuclear DNA fragmentation.