Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation

The only molecular similarity in sex determination found so far among phyla is between the Drosophila doublesex (dsx) and Caenorhabditis elegans mab-3 genes, dsx and mab-3 contain a zinc finger-like DNA-binding motif called t he DM domain, perform several related regulatory functions, and are at leas t partially interchangeable in vivo. A DM domain gene called Dmrt1 has been implicated in male gonad development in a variety of vertebrates, on the b asis of embryonic expression and chromosomal location. Such evidence is hig hly suggestive of a conserved role(s) for Dmrt1 in vertebrate sexual develo pment, but there has been no functional analysis of this gene in any specie s. Here we show that murine Dmrt1 is essential for postnatal testis differe ntiation, with mutant phenotypes similar to those caused by human chromosom e 9p deletions that remove the gene. As in the case of 9p deletions, Dmrt1 is dispensable for ovary development in the mouse. Thus, as in invertebrate s, a DM domain gene regulates vertebrate male development.