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Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice

Item Type:Article
Title:Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice
Creators Name:Kistner, A. and Gossen, M. and Zimmermann, F. and Jerecic, J. and Ullmer, C. and Lubbert, H. and Bujard, H.
Abstract:The tet regulatory system in which doxycycline (dox) acts as an inducer of specifically engineered RNA polymerase II promoters was transferred into transgenic mice. Tight control and a broad range of regulation spanning up to five orders of magnitude were monitored dependent on the dox concentration in the water supply of the animals. Administration of dox rapidly induces the synthesis of the indicator enzyme luciferase whose activity rises over several orders of magnitude within the first 4 h in some organs. Induction is complete after 24 h in most organs analyzed. A comparable regulatory potential was revealed with the tet regulatory system where dox prevents transcription activation. Directing the synthesis of the tetracycline-controlled transactivator (tTA) to the liver led to highly specific regulation in hepatocytes where, in presence of dox, less than one molecule of luciferase was detected per cell. By contrast, a more than 10(5)-fold activation of the luciferase gene was observed in the absence of the antibiotic. This regulation was homogeneous throughout but stringently restricted to hepatocytes. These results demonstrate that both tetracycline-controlled transcriptional activation systems provide genetic switches that permit the quantitative control of gene activities in transgenic mice in a tissue-specific manner and, thus, suggest possibilities for the generation of a novel type of conditional mutants.
Keywords:Cytomegalovirus, Doxycycline, Gene Expression Regulation, Genetic Engineering, In Situ Hybridization, Liver, Genetic Promoter Regions, Messenger RNA, Tissue Distribution, Transcriptional Activation, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences (U.S.A.)
Page Range:10933-10938
Date:1 October 1996
Official Publication:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC38261/?tool=pubmed
PubMed:View item in PubMed

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