Speaking of moon shots, the same issue of Nature has an article on sex determining genes, and guess what. The molecular master switch for controlling the female phenotype is yet another nuclear hormone receptor (IR), which is precisely where 80% of LGND's research effort is directed:
Dax1 antagonizes Sry action in mammalian sex determination
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.
A Swain, V Narvaez, P Burgoyne, G Camerino & R Lovell-Badge
Dax1 antagonizes Sry action in mammalian sex determination
(Article)
Nature 391, 761 (1998) |
