Cdc25b phosphatase is required for resumption of meiosis during oocyte maturation.
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.
Lincoln
A Jeannine
AJ
National Cancer Institute-FCRDC, Frederick, Maryland 21702, USA.
Wickramasinghe
Dineli
D
Stein
Paula
P
Schultz
Richard M
RM
Palko
Mary Ellen
ME
De Miguel
Maria P
MP
Tessarollo
Lino
L
Donovan
Peter J
PJ
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*
D018797:Cell Cycle Proteins; C000715528:Msln protein, mouse; D012333:RNA, Messenger; C517010:Cdc25c protein, mouse; D020687:cdc25 Phosphatases; D000090204:Mesothelin