1. Division of Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
2. Facultad de Ciencias, Universidad Autonoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, CP 62210, Cuernavaca, Morelos, Mexico
3. Biologia Generale e Genetica Medica, Universita di Pavia, via Forlanini 14, 27100 Pavia, Italy

Correspondence to: Robin Lovell-Badge¹ Correspondence and requests for materials should be addressed to R.L.-B.

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.