Endonuclease G is required for early embryogenesis and normal apoptosis in mice
| Autor: | Mei Dong, Jin Dong, Lily Li, Luc Van Kaer, Ming Xu, Danyvid Olivares-Villagómez, James M. Wells, Danwen Lou, Jianhua Zhang, Xiaodong Wang, Yunxia Fan, Purnima Pathre |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
DNA Replication
Male Programmed cell death Mitochondrial DNA ENDOG Apoptosis Biology Transfection DNA Mitochondrial Polymerase Chain Reaction Gene Expression Regulation Enzymologic Embryonic and Fetal Development Mice Pregnancy Testis Animals Fragmentation (cell biology) Cloning Molecular DNA Primers Mice Knockout Multidisciplinary Endodeoxyribonucleases Base Sequence Homozygote Gene Expression Regulation Developmental Biological Sciences Molecular biology Recombinant Proteins Spermatogonia Nuclear DNA Mitochondria Mutagenesis DNA fragmentation Female Mitochondrial DNA replication |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 100(26) |
| ISSN: | 0027-8424 |
| Popis: | 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 thein vivofunction 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+/-thymusin vivocompared 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. |
| Databáze: | OpenAIRE |
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