Disruption of the mouse protein Ser/Thr phosphatase 2Cbeta gene leads to early pre-implantation lethality.
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.
Sasaki
Masato
M
Department of Biochemistry, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryomachi, Aoba-ku, Sendai 980-8575, Japan.
Ohnishi
Motoko
M
Tashiro
Fumi
F
Niwa
Hitoshi
H
Suzuki
Akira
A
Miyazaki
Jun-ichi
J
Kobayashi
Takayasu
T
Tamura
Shinri
S
D000818:Animals; D001483:Base Sequence; D002470:Cell Survival; D010064:Embryo Implantation / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000201:enzymology* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000071636:Protein Phosphatase 2C; D034741:RNA, Small Interfering / Q000494:pharmacology
D034741:RNA, Small Interfering; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C