title: Cdc25b phosphatase is required for resumption of meiosis during oocyte maturation.
abstract: In a wide variety of animal species, oocyte maturation is arrested temporarily at prophase of meiosis I (ref. 1). Resumption of meiosis requires activation of cyclin-dependent kinase-1 (CDK1, p34cdc2), one component of maturation-promoting factor (MPF). The dual specificity phosphatases Cdc25a, Cdc25b and Cdc25c are activators of cyclin-dependent kinases; consequently, they are postulated to regulate cell-cycle progression in meiosis and mitosis as well as the DNA-damage response. We generated Cdc25b-deficient (Cdc25b-/-) mice and found that they are viable. As compared with wildtype cells, fibroblasts from Cdc25b-/- mice grew vigorously in culture and arrested normally in response to DNA damage. Female Cdc25b-/- mice were sterile, and Cdc25b-/- oocytes remained arrested at prophase with low MPF activity. Microinjection of wildtype Cdc25b mRNA into Cdc25b-/- oocytes caused activation of MPF and resumption of meiosis. Thus, Cdc25b-/- female mice are sterile because of permanent meiotic arrest resulting from the inability to activate MPF. Cdc25b is therefore essential for meiotic resumption in female mice. Mice lacking Cdc25b provide the first genetic model for studying the mechanisms regulating prophase arrest in vertebrates.
authors.affiliation: National Cancer Institute-FCRDC, Frederick, Maryland 21702, USA.
authors.forename: A Jeannine
authors.initials: AJ
authors.lastname: Lincoln
authors.forename: Dineli
authors.initials: D
authors.lastname: Wickramasinghe
authors.forename: Paula
authors.initials: P
authors.lastname: Stein
authors.forename: Richard M
authors.initials: RM
authors.lastname: Schultz
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Palko
authors.forename: Maria P
authors.initials: MP
authors.lastname: De Miguel
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Donovan
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology*; D002478:Cells, Cultured; D004249:DNA Damage; D005260:Female; D020935:MAP Kinase Signaling System; D008297:Male; D008540:Meiosis; D000090204:Mesothelin; D051379:Mice; D008856:Microscopy, Fluorescence; D008938:Mitosis; D008957:Models, Genetic; D009865:Oocytes / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000235:genetics* / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; C000715528:Msln protein, mouse; D012333:RNA, Messenger; C517010:Cdc25c protein, mouse; D020687:cdc25 Phosphatases; D000090204:Mesothelin