The protein phosphatase 6 catalytic subunit (Ppp6c) is indispensable for proper post-implantation embryogenesis

Honami Ogoh, Nobuhiro Tanuma, Yasuhisa Matsui, Natsuki Hayakawa, Ayaka Inagaki, Mami Sumiyoshi, Yuki Momoi, Ayako Kishimoto, Mai Suzuki, Nozomi Sasaki, Tsukasa Ohuchi, Miyuki Nomura, Yuriko Teruya, Keiko Yasuda, Toshio Watanabe, Hiroshi Shima

研究成果: Article査読

19 被引用数 (Scopus)


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.

ジャーナルMechanisms of Development
出版ステータスPublished - 2016 2月 1

ASJC Scopus subject areas

  • 胎生学
  • 発生生物学


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