The protein phosphatase 6 catalytic subunit (Ppp6c) is indispensable for proper post-implantation embryogenesis
| Autor: | Keiko Yasuda, Honami Ogoh, Tsukasa Ohuchi, Ayaka Inagaki, Mai Suzuki, Nobuhiro Tanuma, Yuriko Teruya, Hiroshi Shima, Nozomi Sasaki, Mami Sumiyoshi, Natsuki Hayakawa, Miyuki Nomura, Yasuhisa Matsui, Yuki Momoi, Toshio Watanabe, Ayako Kishimoto |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Embryology DNA repair Phosphatase Mutant Embryonic Development Mice Transgenic Biology medicine.disease_cause Embryo Culture Techniques 03 medical and health sciences 0302 clinical medicine Phosphoprotein Phosphatases medicine Animals Inner cell mass Embryo Implantation Blastocyst Protein kinase A Cells Cultured Cell Proliferation Sequence Deletion Mutation Embryo Exons Molecular biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis embryonic structures Female Genes Lethal Developmental Biology |
| Zdroj: | Mechanisms of Development. 139:1-9 |
| ISSN: | 0925-4773 |
| DOI: | 10.1016/j.mod.2016.02.001 |
| Popis: | Ppp6c, which encodes the catalytic subunit of phosphoprotein phosphatase 6 (PP6), is conserved among eukaryotes from yeast to humans. In mammalian cells, PP6 targets IκBε for degradation, activates DNA-dependent protein kinase to trigger DNA repair, and is reportedly required for normal mitosis. Recently, Ppp6c mutations were identified as candidate drivers of melanoma and skin cancer. Nonetheless, little is known about the physiological role of Ppp6c. To investigate this function in vivo, we established mice lacking the Ppp6c phosphatase domain by crossing heterozygous mutants. No viable homozygous pups were born, indicative of a lethal mutation. Ppp6c homozygous mutant embryos were identified among blastocysts, which exhibited a normal appearance, but embryos degenerated by E7.5 and showed clear developmental defects at E8.5, suggesting that mutant embryos die after implantation. Accordingly, homozygous blastocysts showed significant growth failure of the inner cell mass (ICM) in in vitro blastocyst culture, and primary Ppp6c exon4-deficient MEFs showed greatly reduced proliferation. These results establish for the first time that the Ppp6c phosphatase domain is indispensable for mouse embryogenesis after implantation. |
| Databáze: | OpenAIRE |
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