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Publication : Disruption of the mouse protein Ser/Thr phosphatase 2Cbeta gene leads to early pre-implantation lethality.

First Author  Sasaki M Year  2007
Journal  Mech Dev Volume  124
Issue  6 Pages  489-99
PubMed ID  17499977 Mgi Jnum  J:121900
Mgi Id  MGI:3712610 Doi  10.1016/j.mod.2007.04.001
Citation  Sasaki M, et al. (2007) Disruption of the mouse protein Ser/Thr phosphatase 2Cbeta gene leads to early pre-implantation lethality. Mech Dev 124(6):489-99
abstractText  Protein phosphatase 2Cbeta (PP2Cbeta) 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 PP2Cbeta 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 PP2Cbeta 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 PP2Cbeta(Delta/wt) mice generate normal mature gametes. However, PP2Cbeta(Delta/Delta) embryos die between the two-cell and eight-cell stages. To our interest, PP2Cbeta(Delta/Delta) ES cells which had been generated by transfecting PP2Cbeta(3lox/3lox) ES cells with Cre-expressing plasmid were viable. In addition, knockdown of PP2Cbeta using siRNA did not affect the proliferation of wild-type ES cells. These observations suggest that relatively high PP2Cbeta expression is specifically required during the early stages of pre-implantation development. The possible mechanisms for the early pre-implantation lethality of PP2Cbeta(Delta/Delta) mice are discussed.
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