Ecdysone-inducible gene expression in mammalian cells and transgenic mice.
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 tetracycline-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.
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Howard Hughes Medical Institute, Salk Institute for Biomedical Studies, La Jolla, CA 92037, USA.
Yao
T P
TP
Evans
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RM
D000818:Animals; D001483:Base Sequence; D001682:Biological Availability; D002460:Cell Line; D004331:Drosophila melanogaster; D004440:Ecdysone / Q000494:pharmacology*; D004441:Ecdysterone / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011987:Receptors, Steroid / Q000187:drug effects / Q000235:genetics; D013752:Tetracycline / Q000494:pharmacology; D014162:Transfection
D009838:Oligodeoxyribonucleotides; D011987:Receptors, Steroid; C055469:ecdysone receptor; D004440:Ecdysone; C055348:muristerone A; D004441:Ecdysterone; D013752:Tetracycline