Cdk1, but not Cdk2, is the sole Cdk that is essential and sufficient to drive resumption of meiosis in mouse oocytes

被引:112
作者
Adhikari, Deepak [1 ,2 ]
Zheng, Wenjing [1 ]
Shen, Yan [1 ]
Gorre, Nagaraju [1 ,2 ]
Ning, Yao [1 ]
Halet, Guillaume [3 ]
Kaldis, Philipp [4 ]
Liu, Kui [1 ]
机构
[1] Univ Gothenburg, Dept Chem & Mol Biol, SE-40530 Gothenburg, Sweden
[2] Umea Univ, Dept Med Biochem & Biophys, SE-90187 Umea, Sweden
[3] Univ Rennes 1, CNRS, UMR 6061, Inst Genet & Dev Rennes, F-35043 Rennes, France
[4] NUS, A STAR, IMCB, Singapore 138673, Singapore
基金
瑞典研究理事会;
关键词
MATURATION-PROMOTING FACTOR; H-1 HISTONE KINASE; CELL-CYCLE; PROTEIN PHOSPHATASE-1; PHOSPHORYLATION SITES; CRE RECOMBINASE; NUCLEAR LAMINA; PHASE; CDC2; ACTIVATION;
D O I
10.1093/hmg/dds061
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mammalian oocytes are arrested at the prophase of meiosis I during fetal or postnatal development, and the meiosis is resumed by the preovulatory surge of luteinizing hormone. The in vivo functional roles of cyclin-dependent kinases (Cdks) during the resumption of meiosis in mammalian oocytes are largely unknown. Previous studies have shown that deletions of Cdk3, Cdk4 or Cdk6 in mice result in viable animals with normal oocyte maturation, indicating that these Cdks are not essential for the meiotic maturation of oocytes. In addition, conventional knockout of Cdk1 and Cdk2 leads to embryonic lethality and postnatal follicular depletion, respectively, making it impossible to study the functions of Cdk1 and Cdk2 in oocyte meiosis. In this study, we generated conditional knockout mice with oocyte-specific deletions of Cdk1 and Cdk2. We showed that the lack of Cdk1, but not of Cdk2, leads to female infertility due to a failure of the resumption of meiosis in the oocyte. Re-introduction of Cdk1 mRNA into Cdk1-null oocytes largely resumed meiosis. Thus, Cdk1 is the sole Cdk that is essential and sufficient to drive resumption of meiosis in mouse oocytes. We also found that Cdk1 maintains the phosphorylation status of protein phosphatase 1 and lamin A/C in oocytes in order for meiosis resumption to occur.
引用
收藏
页码:2476 / 2484
页数:9
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