Abstract
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.
MeSH terms
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Adherens Junctions / metabolism
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Animals
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Apoptosis / genetics
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Cell Survival / genetics
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DNA Polymerase II / genetics
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DNA Polymerase II / metabolism
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Gene Expression
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Germ Cells / enzymology
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Germ Cells / physiology*
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Gonads / enzymology
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Gonads / metabolism
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Male
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Mice
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Mice, Transgenic
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Mutation
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Organ Specificity
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RNA Interference*
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RNA Precursors / metabolism
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Reproducibility of Results
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Ribonuclease III / metabolism
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Sertoli Cells / metabolism*
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Spermatogenesis / genetics
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Spermatogenesis / physiology*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transfection
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WT1 Proteins / genetics*
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WT1 Proteins / metabolism
Substances
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RNA Precursors
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Transcription Factors
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WT1 Proteins
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DNA Polymerase II
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DROSHA protein, human
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Ribonuclease III