RRC ID 35990
Author Ogoh H, Tanuma N, Matsui Y, Hayakawa N, Inagaki A, Sumiyoshi M, Momoi Y, Kishimoto A, Suzuki M, Sasaki N, Ohuchi T, Nomura M, Teruya Y, Yasuda K, Watanabe T, Shima H.
Title The protein phosphatase 6 catalytic subunit (Ppp6c) is indispensable for proper post-implantation embryogenesis.
Journal Mech Dev
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.
Volume 139
Pages 1-9
Published 2016-2-1
DOI 10.1016/j.mod.2016.02.001
PII S0925-4773(16)30004-1
PMID 26868000
MeSH Animals Blastocyst / cytology Blastocyst / enzymology Cell Proliferation Cells, Cultured Embryo Culture Techniques Embryo Implantation Embryonic Development Exons Female Genes, Lethal Male Mice, Inbred C57BL Mice, Transgenic Phosphoprotein Phosphatases / physiology* Sequence Deletion
IF 2.176
Times Cited 10
Mice B6.Cg-Tg(CAG-Cre)CZ-MO2Osb(RBRC01828)