Inhibition of MEK or cdc2 Kinase Parthenogenetically Activates Mouse Eggs and Yields the Same Phenotypes as Mos−/− Parthenogenotes

Developmental Biology

Karen P. Phillips¹  Jennifer L. Collins¹  Mary Ann F. Petrunewich¹  X.Johné Liu¹  Jay M. Baltz¹  Ronald A. Booth¹ 

[1] Ottawa Health Research Institute, University of Ottawa

关键词: mouse eggs;    U0126;    MEK;    MAPK;    roscovitine;    MPF;    parthenogenetic activation;    fertilization;    egg activation;   

DOI  :  10.1006/dbio.2002.0680

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

MammalianeggsarearrestedinmetaphaseIIofmeiosisuntilfertilization.Arrestismaintainedbycytostaticfactor(CSF)activity,whichisdependentontheMOS–MEK–MAPKpathway.InhibitionofMEK1/2withaspecificinhibitor,U0126,parthenogeneticallyactivatedmouseeggs,producingphenotypessimilartoMos−/−parthenogenotes(premature,unequalcleavagesandlargepolarbodies).U0126inactivatedMAPKineggswithin1h,incontrasttothe5hrequiredafterfertilization,whilethetimecourseofMPFinactivationwassimilarinU0126-activatedandfertilizedeggs.WealsofoundthatinactivationofMPFbythecdc2kinaseinhibitorroscovitineinducedparthenogeneticactivation.InactivationofMPFbyroscovitineresultedinthesubsequentinactivationofMAPKwithatimecoursesimilartothatfollowingfertilization.Notably,roscovitinealsoproducedsomeMos−/−-likephenotypes,indistinguishablefromU0126parthenogenotes.SimultaneousinhibitionofbothMPFandMAPKineggstreatedwithroscovitineandU0126producedaveryhighproportionofeggswiththemoreseverephenotype.ThesefindingsconfirmthatMEKisarequiredcomponentofCSFinmammalianeggsandimplythatthesequentialinactivationofMPFfollowedbyMAPKinactivationisrequiredfornormalspindlefunctionandpolarbodyemission.

【 授权许可】

Unknown