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

Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation
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DOI:
10.1101/gad.834100
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发表时间:
2000-10-15
影响因子:
10.5
通讯作者:
Zarkower, D
Zarkower, D
中科院分区:
生物学1区
文献类型:
--
作者:
Raymond, CS;Murphy, MW;Zarkower, D

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迄今为止,在门中发现的性别决定的唯一分子相似性是在果蝇doubla ex(dsx)和秀丽隐杆线虫(Caillhabditis elegans)的mAb-3基因之间,dsx和mAb-3含有称为DM结构域的锌指样DNA结合基序,执行几种相关的调节功能,并且在体内至少部分可互换。DM域基因Dmrt 1已被牵连在雄性性腺发育的各种脊椎动物,胚胎表达和染色体定位的基础上。这些证据高度提示了Dmrt 1在脊椎动物性发育中的保守作用,但在任何物种中都没有对该基因进行功能分析。在这里,我们表明,小鼠Dmrt 1是出生后睾丸分化所必需的,与人类染色体9 p缺失,删除基因所造成的突变表型相似。与9 p缺失的情况一样,Dmrt 1在小鼠卵巢发育中是不稳定的。因此,在无脊椎动物中,DM结构域基因调节脊椎动物雄性发育。
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.