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The Wilms tumor gene, Wt1, is required for Sox9 expression and maintenance of tubular architecture in the developing testis.

Mutation of the transcription factor and tumor suppressor gene WT1 results in a range of genitourinary anomalies in humans, including 46,XY gonadal dysgenesis, indicating that WT1 plays a critical role in sex determination. However, because knockout of Wt1 in mice results in apoptosis of the genital ridge, it is unknown whether WT1 is required for testis development after the initial steps of sex determination. To address this question, we generated a mouse strain carrying a Wt1 conditional knockout allele and ablated Wt1 function specifically in Sertoli cells by embryonic day 14.5, several days after testis determination. Wt1 knockout resulted in disruption of developing seminiferous tubules and subsequent progressive loss of Sertoli cells and germ cells such that postnatal mutant testes were almost completely devoid of these cell types and were severely hypoplastic. Thus, Wt1 is essential for the maintenance of Sertoli cells and seminiferous tubules in the developing testes. Of particular note, expression of the testis-determining gene Sox9 in mutant Sertoli cells was turned off at embryonic day 14.5 after Wt1 ablation, suggesting that WT1 regulates Sox9, either directly or indirectly, after Sry expression ceases. Our data, along with previous work demonstrating the role of Wt1 at early stages of gonadal development, thus indicate that Wt1 is essential at multiple steps in testicular development.

Pubmed ID: 16877546 RIS Download

Mesh terms: Alleles | Animals | Gene Expression Regulation, Developmental | High Mobility Group Proteins | Male | Mice | Mice, Knockout | Mutation | SOX9 Transcription Factor | Sertoli Cells | Testis | Transcription Factors | WT1 Proteins | Wilms Tumor

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Associated grants

  • Agency: NICHD NIH HHS, Id: HD30284
  • Agency: NCI NIH HHS, Id: P30 CA016672
  • Agency: NCI NIH HHS, Id: CA16672
  • Agency: NCI NIH HHS, Id: R01 CA078257
  • Agency: NCI NIH HHS, Id: CA34936
  • Agency: NCI NIH HHS, Id: CA78257
  • Agency: NICHD NIH HHS, Id: R37 HD030284
  • Agency: NICHD NIH HHS, Id: R01 HD030284
  • Agency: NCI NIH HHS, Id: P01 CA034936

Mouse Genome Informatics (Data, Gene Annotation)

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