Program in Molecular Medicine; Department of Medicine, Division of Diabetes
Animals; Blotting, Western; DNA Primers; Female; Intercellular Signaling Peptides and Proteins; Mice; Mice, Transgenic; Models, Biological; Oocytes; Ovarian Follicle; RNA, Messenger; RNA, Small Interfering; RNA-Binding Proteins; Reverse Transcriptase Polymerase Chain Reaction
Endocrine System Diseases | Endocrinology, Diabetes, and Metabolism | Molecular Biology
CPEB is a sequence-specific RNA-binding protein that regulates polyadenylation-induced translation. In Cpeb knockout mice, meiotic progression is disrupted at pachytene due to inhibited translation of synaptonemal complex protein mRNAs. To assess the function of CPEB after pachytene, we used the zona pellucida 3 (Zp3) promoter to generate transgenic mice expressing siRNA that induce the destruction of Cpeb mRNA. Oocytes from these animals do not develop normally; they undergo parthenogenetic cell division in the ovary, exhibit abnormal polar bodies, are detached from the cumulus granulosa cell layer, and display spindle and nuclear anomalies. In addition, many follicles contain apoptotic granulosa cells. CPEB binds several oocyte mRNAs, including Smad1, Smad5, spindlin, Bub1b, Mos, H1foo, Obox1, Dnmt1o, TiParp, Trim61 and Gdf9, a well described oocyte-expressed growth factor that is necessary for follicle development. In Cpeb knockdown oocytes, Gdf9 RNA has a shortened poly(A) tail and reduced expression. These data indicate that CPEB controls the expression of Gdf9 mRNA, which in turn is necessary for oocyte-follicle development. Finally, several phenotypes, i.e. progressive oocyte loss and infertility, elicited by the knockdown of CPEB in oocytes resemble those of the human premature ovarian failure syndrome.
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Citation: Development. 2006 Nov;133(22):4527-37. Epub 2006 Oct 18. Link to article on publisher's site
DOI of Published Version
Development (Cambridge, England)
Waldemar, Racki J. and Richter, Joel D., "CPEB controls oocyte growth and follicle development in the mouse" (2006). Open Access Articles. 475.