Use of the tetracycline-controlled transcriptional silencer (tTS) to eliminate transgene leak in inducible overexpression transgenic mice

The Journal of Biological Chemistry
Z ZhuJack A Elias

Abstract

The doxycycline-inducible reverse tetracycline transactivator (rtTA) is frequently used to overexpress transgenes in a temporally regulated fashion in vivo. These systems are, however, often limited by the levels of transgene expression in the absence of dox administration. The tetracycline-controlled transcriptional silencer (tTS), a fusion protein containing the tet repressor and the KRAB-AB domain of the kid-1 transcriptional repressor, is inhibited by doxycycline. We hypothesized that tTS would tighten control of transgene expression in rtTA-based systems. To test this hypothesis we generated mice in which the CC10 promoter targeted tTS to the lung, bred these mice with CC10-rtTA-interleukin 13 (IL-13) mice in which IL-13 was overexpressed in an inducible lung-specific fashion, and compared the IL-13 production and phenotypes of parental mice and the triple transgenic CC10-rtTA/tTS-IL-13 progeny of these crosses. In the CC10-rtTA-IL-13 mice, IL-13, mucus metaplasia, inflammation, alveolar enlargement, and enhanced lung volumes were noted at base line and increased greatly after doxycycline administration. In the triple transgenic tTS animals, IL-13 and the IL-13-induced phenotype could not be appreciated without doxycycline...Continue Reading

References

Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M Gossen, H Bujard
Jul 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·P ShockettD G Schatz
Apr 11, 1995·Proceedings of the National Academy of Sciences of the United States of America·S EfratX Wang
Apr 1, 1995·Molecular and Cellular Biology·U DeuschleH J Thiesen
Sep 27, 1994·Proceedings of the National Academy of Sciences of the United States of America·P A FurthL Hennighausen
Dec 1, 1993·Trends in Biochemical Sciences·M GossenH Bujard
May 10, 1994·Proceedings of the National Academy of Sciences of the United States of America·R WitzgallJ V Bonventre
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·A KistnerH Bujard
May 16, 1998·Oncogene·G L Gallia, K Khalili
Sep 2, 1998·The Journal of Allergy and Clinical Immunology·J E de Vries
Dec 18, 1998·Science·M Wills-KarpD D Donaldson
Feb 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·U BaronH Bujard
Apr 15, 2000·The Journal of Biological Chemistry·J W TichelaarJ A Whitsett
Apr 27, 2000·American Journal of Respiratory Cell and Molecular Biology·N S WardJ A Elias
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·S UrlingerW Hillen
Dec 6, 2000·The Journal of Experimental Medicine·Z WangJ A Elias

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Citations

Oct 15, 2008·Transgenic Research·Yan An WangZhi Yuan Zhang
Apr 20, 2005·Neurobiology of Disease·Witold KonopkaLeszek Kaczmarek
Dec 3, 2002·Current Opinion in Biotechnology·Stéphane Y Corbel, Fabio M V Rossi
Jul 20, 2002·Seminars in Cell & Developmental Biology·Zhou ZhuJack A Elias
Sep 21, 2002·Seminars in Cell & Developmental Biology·Chris AlbaneseRichard G Pestell
Dec 7, 2002·The International Journal of Biochemistry & Cell Biology·Ying-yi XiaoNeil E Forsberg
Apr 20, 2002·Drug Discovery Today·Jan Törnell, Michael Snaith
Oct 26, 2005·Nature Medicine·Dianhua JiangPaul W Noble
Jun 15, 2011·Proceedings of the National Academy of Sciences of the United States of America·William E LawsonTimothy S Blackwell
Jun 12, 2003·Nucleic Acids Research·Christel KruegerWolfgang Hillen
Aug 11, 2012·Nucleic Acids Research·Ruilin SunJian Fei
Apr 27, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jae-Kyun KoJianjie Ma
Feb 24, 2004·Annual Review of Physiology·I KwakF J DeMayo
Dec 20, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jennifer A JohnsonJames West
Dec 6, 2001·American Journal of Respiratory and Critical Care Medicine·Z ZhuJ A Elias
Feb 12, 2008·American Journal of Respiratory and Critical Care Medicine·Cristen PantanoYvonne M W Janssen-Heininger
Oct 3, 2003·American Journal of Respiratory and Critical Care Medicine·Moisés Selman
Dec 24, 2002·American Journal of Respiratory Cell and Molecular Biology·Jeffrey J Atkinson, Robert M Senior
Aug 31, 2004·American Journal of Respiratory Cell and Molecular Biology·Alfin G VicencioJack A Elias
Oct 13, 2007·American Journal of Respiratory Cell and Molecular Biology·Masashi YamasakiChun Geun Lee
Apr 17, 2010·American Journal of Respiratory Cell and Molecular Biology·Julia DuerrMarcus A Mall
Dec 14, 2011·American Journal of Respiratory Cell and Molecular Biology·Dianhua JiangPaul W Noble
Oct 29, 2011·American Journal of Respiratory Cell and Molecular Biology·Corina N D'Alessandro-GabazzaEsteban C Gabazza
Sep 27, 2012·Endocrinology·Xiujun FanNihar R Nayak
Aug 1, 2008·Journal of the American Society of Nephrology : JASN·Liming WangRobert F Spurney
May 19, 2011·Yi chuan = Hereditas·Fu-Yu Lin, Xiao Yang
Nov 12, 2013·Transgenic Research·Fabien DelerueLars M Ittner
Dec 1, 2004·Proceedings of the National Academy of Sciences of the United States of America·Quan LuStanley N Cohen
Oct 26, 2013·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Qilin GuZongbin Cui
Aug 4, 2007·Clinical and Experimental Immunology·G Y ParkJ W Christman
Jun 25, 2013·Biotechnology and Bioengineering·Yuichiro ToneTeruyuki Nagamune
May 8, 2010·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Y BosséM Rola-Pleszczynski
Jul 14, 2004·Brain Research. Molecular Brain Research·Mossa Gardaneh, Karen L O'Malley
Apr 10, 2013·Gene·Agnieszka JazwaJozef Dulak

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