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    CPEB controls oocyte growth and follicle development in the mouse

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    Authors
    Waldemar, Racki J.
    Richter, Joel D.
    UMass Chan Affiliations
    Department of Medicine, Division of Diabetes
    Program in Molecular Medicine
    Document Type
    Journal Article
    Publication Date
    2006-10-20
    Keywords
    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
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    Abstract
    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.
    Source
    Development. 2006 Nov;133(22):4527-37. Epub 2006 Oct 18. Link to article on publisher's site
    DOI
    10.1242/dev.02651
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/41945
    PubMed ID
    17050619
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1242/dev.02651
    Scopus Count
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