Targeted mutagenesis of the endogenous mouse Mis gene promoter:: In vivo definition of genetic pathways of vertebrate sexual development
Targeted mutagenesis of the endogenous mouse Mis gene promoter:: In vivo definition of genetic pathways of vertebrate sexual development
复制标题
DOI：
10.1016/s0092-8674(00)81527-5
复制
发表时间：
1999-11-12
期刊：
影响因子：
64.5
通讯作者：
Behringer, RR
中科院分区：
文献类型：
--
作者：
Arango, NA;Lovell-Badge, R;Behringer, RR
突变被引入内源性小鼠缪勒管抑制物质（Mis）启动子中保守的甾体生成因子1 (SF1)-和sox9结合位点。突变sf1结合位点纯合的雄性小鼠在胎儿睾丸中正确启动了Mis转录，尽管其水平显著降低。令人惊讶的是，产生了足够的MIS来消除缪勒管。相比之下，突变sox9结合位点的雄性纯合子没有启动Mis转录，导致假雌雄同体。这些研究表明，SOX9在Mis转录起始中起重要作用，而SF1似乎是Mis转录水平的定量调节剂，可能影响非苗勒管组织。在脊椎动物中Mis表达的比较研究表明，Mis启动子接受不同物种的转录输入，但产生相同的功能读数。
Mutations were introduced into conserved steroidogenic factor 1 (SF1)- and SOX9-binding sites within the endogenous mouse Mullerian inhibiting substance (Mis) promoter. Male mice homozygous for the mutant SF1-binding site correctly initiated Mis transcription in fetal testes, although at significantly reduced levels. Surprisingly, sufficient MIS was produced to eliminate the Mullerian ducts. In contrast, males homozygous for the mutant SOX9-binding site did not initiate Mis transcription, resulting in pseudohermaphrodites. These studies suggest an essential role for SOX9 in the initiation of Mis transcription, whereas SF1 appears to act as a quantitative regulator of Mis transcript levels, perhaps for influencing non-Mullerian duct tissues. Comparative studies of Mis expression in vertebrates indicate that the Mis promoter receives transcriptional inputs that vary between species but result in the same functional readout.