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 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.
Raymond
C S
CS
Graduate Program in Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Murphy
M W
MW
O'Sullivan
M G
MG
Bardwell
V J
VJ
Zarkower
D
D
D000818:Animals; D029742:Caenorhabditis elegans Proteins; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D005260:Female; D017353:Gene Deletion; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008540:Meiosis; D051379:Mice; D008817:Mice, Mutant Strains; D010053:Ovary / Q000166:cytology / Q000254:growth & development; D012708:Sertoli Cells / Q000473:pathology; D013737:Testis / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C110547:DMRT1 protein; D004268:DNA-Binding Proteins; C070369:DSX protein, Drosophila; D029721:Drosophila Proteins; D015801:Helminth Proteins; D019476:Insect Proteins; C110548:Mab-3 protein, C elegans; D014157:Transcription Factors