LAUSR

Mammalian oocytes are arrested at meiotic prophase I. The dual-specificity phosphatase CDC25B is essential for cyclin-dependent kinase 1 (CDK1) activation that drives resumption of meiosis. CDC25B reverses the inhibitory effect of the protein kinases WEE1/MYT1 on CDK1 activation. Cdc25b-/- female mice are infertile because oocytes cannot activate CDK1. To identify a role for CDC25B following resumption of meiosis, we restored CDK1 activation in Cdc25b-/- oocytes by inhibiting WEE1/MYT1, or expressing EGFP-CDC25A or constitutively active EGFP-CDK1 from microinjected cRNAs. Forced CDK1 activation in Cdc25b-/- oocytes allowed resumption of meiosis, but oocytes mostly arrested at metaphase I (MI) with intact spindles. Similarly, ∼1/3 of Cdc25b+/- oocytes with reduced amount of CDC25B arrest in MI. MI arrested Cdc25b-/- oocytes also display a transient decrease in CDK1 activity similar to Cdc25b+/+ oocytes during the MI-MII transition, whereas Cdc25b+/- oocytes exhibit only a partial APC/C activation and anaphase I entry. Thus, CDC25B is necessary for resumption of meiosis and the MI-MII transition.