Dax1 antagonizes Sry action in mammalian sex determination

Amanda Swain, Veronica Narvaez, Paul Burgoyne, Giovanna Camerino and Robin Lovell-Badge
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Amanda Swain: MRC National Institute for Medical Research
Veronica Narvaez: MRC National Institute for Medical Research
Paul Burgoyne: MRC National Institute for Medical Research
Giovanna Camerino: Biologia Generale e Genetica Medica, Universita di Pavia
Robin Lovell-Badge: MRC National Institute for Medical Research

Nature, 1998, vol. 391, issue 6669, 761-767

Abstract: 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.

Date: 1998
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DOI: 10.1038/35799

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