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Dax1 antagonizes Sry action in mammalian sex determination

Nature volume 391, pages 761767 (19 February 1998) | Download Citation

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Abstract

DAX1, which encodes an unusual member of the nuclear hormone-receptor superfamily, is a gene that may be responsible for a sex-reversal syndrome in humans, referred to as dosage-sensitive sex reversal, in which XY individuals carrying duplications of Xp21, part of the small arm of the X chromosome, develop as females. XY mice carrying extra copies of mouse Dax1 as a transgene show delayed testis development when the gene is expressed at high levels, but do not normally show sex reversal. Complete sex reversal occurs, however, when the transgene is tested against weak alleles of the sex-determining Y-chromosome gene Sry. These results show that DAX1 is largely, if not solely, responsible for dosage-sensitive sex reversal and provide a model for early events in mammalian sex determination, when precise levels and timing of gene expression are critical.

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Acknowledgements

We thank members of R.L.B.'s laboratory and B. Capel for suggestions, P.Sassone-Corsi for anti-DAX1 antibody, E. Zanaria for genomic and cDNA probes, E. Grigorieva for help with histological analysis, K. Woolley and C. Wise for help with mouse genotyping, the animal caretakers at NIMR, and J. Brock for photography. The financial support from the MRC and Louis Jeantet Foundation (R.L.-B.), the DGAPA-UNAM, Mexico and the British Council (V.N.), and Telethon, Italy and the European Commission (G.C.) is gratefully acknowledged.

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Affiliations

  1. *Division of Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK

    • Amanda Swain
    • , Veronica Narvaez
    • , Paul Burgoyne
    •  & Robin Lovell-Badge
  2. †Facultad de Ciencias, Universidad Autonoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, CP 62210, Cuernavaca, Morelos, Mexico

    • Veronica Narvaez
  3. ‡Biologia Generale e Genetica Medica, Universita di Pavia, via Forlanini 14, 27100 Pavia, Italy

    • Giovanna Camerino

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Correspondence to Robin Lovell-Badge.

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https://doi.org/10.1038/35799

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