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    Genes Dev. 2006 Jan 15;20(2):147-52.

    Tissue-specific RNAi reveals that WT1 expression in nurse cells controls germ cell survival and spermatogenesis.

    Rao MK, Pham J, Imam JS, MacLean JA, Murali D, Furuta Y, Sinha-Hikim AP, Wilkinson MF.

    Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

    Using a novel tissue-specific RNA interference (RNAi) approach that mimics the principle by which naturally occurring microRNAs (miRNA) are made, we demonstrate that the Wilms' tumor 1 (WT1) transcription factor has an essential role in spermatogenesis. Mice depleted of WT1 in Sertoli nurse cells suffered from increased germ cell apoptosis, loss of adherens junctions, disregulation of adherence junction-associated genes, and impaired fertility. These effects were recapitulated in transgenic mice expressing a dominant-negative form of WT1 in Sertoli cells, demonstrating the validity of our RNAi approach. Our results indicate that the tumor suppressor WT1 promotes Sertoli cell-germ cell signaling events driving spermatogenesis.

    PMID: 16418481 [PubMed - indexed for MEDLINE]

    PMCID: 1356106

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