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Vol. 14, No. 20, pp. 2587-2595, October 15, 2000
1 Graduate Program in Biochemistry, Molecular Biology and
Biophysics, 2 Department of Genetics, Cell Biology, and Development,
3 Department of Veterinary Medicine and Pathology, 4 Cancer
Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
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 the
DM domain, perform several related regulatory functions, and are at
least partially interchangeable in vivo. A DM domain gene called
Dmrt1 has been implicated in male gonad development in a
variety of vertebrates, on the basis of embryonic expression and
chromosomal location. Such evidence is highly suggestive of a conserved
role(s) for Dmrt1 in vertebrate sexual development, but there
has been no functional analysis of this gene in any species. Here we
show that murine Dmrt1 is essential for postnatal testis
differentiation, with mutant phenotypes similar to those caused by
human chromosome 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 invertebrates, a DM domain gene regulates vertebrate
male development.
[Key Words: DM domain; Dmrt1; sex determination; doublesex; mab-3]
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