title: The protein phosphatase 6 catalytic subunit (Ppp6c) is indispensable for proper post-implantation embryogenesis.
abstract: 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.
authors: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
authors: Honami
authors: H
authors: Ogoh
authors: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Japan.
authors: Nobuhiro
authors: N
authors: Tanuma
authors: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors: Yasuhisa
authors: Y
authors: Matsui
authors: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
authors: Natsuki
authors: N
authors: Hayakawa
authors: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
authors: Ayaka
authors: A
authors: Inagaki
authors: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
authors: Mami
authors: M
authors: Sumiyoshi
authors: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Japan.
authors: Yuki
authors: Y
authors: Momoi
authors: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
authors: Ayako
authors: A
authors: Kishimoto
authors: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
authors: Mai
authors: M
authors: Suzuki
authors: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Japan.
authors: Nozomi
authors: N
authors: Sasaki
authors: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Japan.
authors: Tsukasa
authors: T
authors: Ohuchi
authors: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Japan.
authors: Miyuki
authors: M
authors: Nomura
authors: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
authors: Yuriko
authors: Y
authors: Teruya
authors: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
authors: Keiko
authors: K
authors: Yasuda
authors: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan. Electronic address: shima@med.tohoku.ac.jp.
authors: Toshio
authors: T
authors: Watanabe
authors: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Japan. Electronic address: toshiwatana@cc.nara-wu.ac.jp.
authors: Hiroshi
authors: H
authors: Shima
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000201:enzymology; D049109:Cell Proliferation; D002478:Cells, Cultured; D046149:Embryo Culture Techniques; D010064:Embryo Implantation; D047108:Embryonic Development; D005091:Exons; D005260:Female; D005804:Genes, Lethal; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D017384:Sequence Deletion
chemical_list: D010749:Phosphoprotein Phosphatases; C106079:protein phosphatase 6
keywords: Embryogenesis; Growth failure; Inner cell mass (ICM); MEFs; Post-implantation; Protein phosphatase 6 catalytic subunit (Ppp6c)