Disruption of the mouse protein Ser/Thr phosphatase 2Cβ gene leads to early pre-implantation lethality

Masato Sasaki, Motoko Ohnishi, Fumi Tashiro, Hitoshi Niwa, Akira Suzuki, Jun ichi Miyazaki, Takayasu Kobayashi, Shinri Tamura

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Protein phosphatase 2Cβ (PP2Cβ) is a member of a family of protein Ser/Thr phosphatases (PP2C) that is composed of at least twelve different gene products. Recent studies have revealed that PP2Cβ mRNA accumulates in mature sperm, unfertilized metaphase II-arrested oocytes and zygotes, but that the mRNA level then decreases sharply between the early two-cell and eight-cell stages, remaining at low levels during the 16-cell to blastocyst stages of mice. These observations raised the possibility that PP2Cβ plays a crucial role during gametogenesis, fertilization, and/or early stages of embryonic development. In this study, we employed a gene knockout technique in mice to test this possibility. We found that PP2CβΔ/wt mice generate normal mature gametes. However, PP2CβΔ/Δ embryos die between the two-cell and eight-cell stages. To our interest, PP2CβΔ/Δ ES cells which had been generated by transfecting PP2Cβ3lox/3lox ES cells with Cre-expressing plasmid were viable. In addition, knockdown of PP2Cβ using siRNA did not affect the proliferation of wild-type ES cells. These observations suggest that relatively high PP2Cβ expression is specifically required during the early stages of pre-implantation development. The possible mechanisms for the early pre-implantation lethality of PP2CβΔ/Δ mice are discussed.

Original languageEnglish
Pages (from-to)489-499
Number of pages11
JournalMechanisms of Development
Volume124
Issue number6
DOIs
Publication statusPublished - 2007 Jul

Keywords

  • ES cell
  • Gene knockout
  • Pre-implantation lethality
  • Protein phosphatase 2C
  • p38
  • siRNA

ASJC Scopus subject areas

  • Embryology
  • Developmental Biology

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