Ecdysone-inducible gene expression in mammalian cells and transgenic mice

Ecdysone-inducible gene expression in mammalian cells and transgenic mice
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DOI:
10.1073/pnas.93.8.3346
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发表时间:
1996-04-16
影响因子:
11.1
通讯作者:
Evans, RM
Evans, RM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
No, D;Yao, TP;Evans, RM

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被引文献

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在果蝇的变态过程中,一系列的形态变化是由类固醇激素20-OH蜕皮激素通过蜕皮激素受体,核受体超家族的成员,在这份报告中,我们已经转移昆虫激素的反应,哺乳动物细胞的稳定表达的修饰的蜕皮激素受体,调节优化的蜕皮激素响应启动子。在用激素处理时已经实现了达到4个数量级的诱导。表达修饰的蜕皮激素受体的转基因小鼠在施用激素时可以激活整合的蜕皮激素应答启动子。基于四环素和基于蜕皮激素的诱导系统的比较揭示了蜕皮激素调节系统表现出较低的基础活性和较高的诱导性。由于蜕皮激素给药对哺乳动物没有明显的影响,它用于调节基因对于转基因小鼠中任何基因的瞬时诱导表达和基因治疗应该是极好的。
During metamorphosis of Drosophila melanogaster, a cascade of morphological changes is triggered by the steroid hormone 20-OH ecdysone via the ecdysone receptor, a member of the nuclear receptor superfamily, In this report, we have transferred insect hormone responsiveness to mammalian cells by the stable expression of a modified ecdysone receptor that regulates an optimized ecdysone responsive promoter. Inductions reaching 4 orders of magnitude have been achieved upon treatment with hormone, Transgenic mice expressing the modified ecdysone receptor can activate an integrated ecdysone responsive promoter upon administration of hormone. A comparison of tetracyline-based and ecdysone-based inducible systems reveals the ecdysone regulatory system exhibits lower basal activity and higher inducibility. Since ecdysone administration has no apparent effect on mammals, its use for regulating genes should be excellent for transient inducible expression of any gene in transgenic mice and for gene therapy.