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

Mech Dev. 2016 Feb:139:1-9. doi: 10.1016/j.mod.2016.02.001. Epub 2016 Feb 8.

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.

Keywords: Embryogenesis; Growth failure; Inner cell mass (ICM); MEFs; Post-implantation; Protein phosphatase 6 catalytic subunit (Ppp6c).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Phosphoprotein Phosphatases
  • protein phosphatase 6