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Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter

Item Type:Article
Title:Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter
Creators Name:Furth, P.A. and Onge, S.T. and Boger, H. and Gruss, P. and Gossen, M. and Kistner, A. and Bujard, H. and Hennighausen, L.
Abstract:Promoters whose temporal activity can be directly manipulated in transgenic animals provide a tool for the study of gene functions in vivo. We have evaluated a tetracycline-responsive binary system for its ability to temporally control gene expression in transgenic mice. In this system, a tetracycline-controlled trans-activator protein (tTA), composed of the repressor of the tetracycline-resistance operon (tet from Escherichia coli transposon Tn10) and the activating domain of viral protein VP16 of herpes simplex virus, induces transcription from a minimal promoter (PhCMV*-1; see below) fused to seven tet operator sequences in the absence of tetracycline but not in its presence. Transgenic mice were generated that carried either a luciferase or a beta-galactosidase reporter gene under the control of PhCMV*-1 or a transgene containing the tTA coding sequence under the control of the human cytomegalovirus immediate early gene 1 (hCMV IE1) promoter/enhancer. Whereas little luciferase or beta-galactosidase activity was observed in tissues of mice carrying only the reporter genes, the presence of tTA in double-transgenic mice induced expression of the reporter genes up to several thousand-fold. This induction was abrogated to basal levels upon administration of tetracycline. These findings can be used, for example, to design dominant gain-of-function experiments in which temporal control of transgene expression is required.
Keywords:Base Sequence, Cytomegalovirus, DNA Primers, DNA Transposable Elements, Mammalian Embryo, Genetic Enhancer Elements, Escherichia Coli, Gene Expression, Gestational Age, Luciferases, Molecular Sequence Data, Muscles, Operon, Organ Specificity, Polymerase Chain Reaction, Genetic Promoter Regions, Simplexvirus, Tetracycline, Time Factors, Tongue, Trans-Activators, beta-Galactosidase
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
Page Range:9302-9306
Date:27 September 1994
Official Publication:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC44800/?tool=pubmed
PubMed:View item in PubMed

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