Transgenic Research

, Volume 14, Issue 5, pp 691–702 | Cite as

Gonadal Effects of a Mouse Denys-Drash Syndrome Mutation

  • C.E. Patek
  • P.T.K. Saunders
  • C.G. Miles
  • R.L. Berry
  • N.D. Hastie
  • R.M. Sharpe
  • M.L. HooperEmail author


Gonadal effects of the Denys-Drash syndrome (DDS) mutation Wt1tmT396 were examined in chimaeric and heterozygous mice. Since the only heterozygote was 41,XXY, Sertoli cell function was assessed by comparison with age-matched control XXY testes. Control XXY Sertoli cells showed immunoexpression of WT1 and androgen receptor (AR) indistinguishable from wild-type (40,XY), but expressed anti-Mullerian hormone (AMH). In contrast, DDS Sertoli cells showed only faint immunoexpression of WT1 and did not express AR or AMH. While XY↔XY DDS chimaeras were male, XX↔XY chimaeras were predominantly female. In the rare XX↔XY DDS males the Sertoli cell lineage was largely derived from Wt1 mutant XY cells. We conclude that DDS mutant cells can form Sertoli cells, that the dominant mutation does not cause male sex reversal in mice but distorts the sex ratio of XX↔XY chimaeras, and that there may be a link between WT1, AMH and AR expression by Sertoli cells in vivo.


androgen receptor anti-Mullerian hormone Denys-Drash syndrome Sertoli cell sex chimaerism WT1 


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Copyright information

© Springer 2005

Authors and Affiliations

  • C.E. Patek
    • 1
  • P.T.K. Saunders
    • 2
  • C.G. Miles
    • 3
    • 4
  • R.L. Berry
    • 1
    • 3
  • N.D. Hastie
    • 3
  • R.M. Sharpe
    • 2
  • M.L. Hooper
    • 1
    Email author
  1. 1.Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine CentreWestern General HospitalEdinburghUK
  2. 2.MRC Human Reproductive Sciences UnitCentre for Reproductive BiologyEdinburghUK
  3. 3.MRC Human Genetics UnitWestern General HospitalEdinburghUK
  4. 4.Institute of Human GeneticsInternational Centre for LifeNewcastle-upon-TyneUK

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