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Transcriptional Activation by Tetracyclines in Mammalian Cells
Abstract
A transcriptional transactivator was developed that fuses the VP16 activation domain with a mutant Tet repressor from Escherichia coli. This transactivator requires certain tetracycline (Tc) derivatives for specific DNA binding. Thus, addition of doxycycline to HeLa cells that constitutively synthesized the transactivator and that contained an appropriate, stably integrated reporter unit rapidly induced gene expression more than a thousandfold. The specificity of the Tet repressor-operator-effector interaction and the pharmacological characteristics of Tc's make this regulatory system well suited for the control of gene activities in vivo, such as in transgenic animals and possibly in gene therapy.
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“In 1995, Gossen et al. developed the Tet-On system (Fig. 1C), a regulatory system that allows activation of gene expression by the addition - instead of removal - of dox [12].”
From Tet-On Systems For Doxycycline-inducible Gene Expression (2016) · cites this paper as [12]
In the citing paper
“This reverse-TetR (rTetR) differed at four amino acid positions from the original protein (Fig. 2).”
From Tet-On Systems For Doxycycline-inducible Gene Expression (2016) · cites this paper as [12]
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Tight control of gene expression in mammalian cells by tetracycline-responsive promoters.
Gossen, M., & Bujard, H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.12.5547 · Cited by 4,943
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- 10.1016/0003-2697(83)90418-9 · DOI
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“Recent sophistication of molecular genetic techniques has made it possible to circumvent such potential problems by spatiotemporally regulating a gene-targeting or transgene expression (Moller, 1994; Kühn et al., 1995; Gossen et al., 1995; Rajewsky et al., 1996, Son and Joh, 1997; Rohrer and Kobilka, 1998).”
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“[123] Gossen M, Freundlieb S, Bender G, Muller G, Hillen W,”
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Niemann, H., & Kues, W. A. (2003) · Animal Reproduction Science · doi:10.1016/s0378-4320(03)00169-6 · Cited by 154
“the presence of a tetracycline analogue led to a burst of expression in cell lines and even transgenic mice (Tet-on) (Gossen et al., 1995).”
BackgroundMethodExpanding the Repertoire of Optogenetically Targeted Cells with an Enhanced Gene Expression System
Tanaka, K. F., Matsui, K., Sasaki, T., Sano, H., Sugio, S., Fan, K., Hen, R., Nakai, J., Yanagawa, Y., Hasuwa, H., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.06.011 · Cited by 183
“We instead used a bigenic approach involving a tet-inducible promoter system (Gossen et al., 1995).”
MethodA New-Generation Stable Inducible Packaging Cell Line for Lentiviral Vectors
Farson, D. A., Witt, R. M., MCGUINNESS, R. P., Dull, T., Kelly, M., Song, J., Radeke, R., Bukovsky, A., Consiglio, A., & Naldini, L. (2001) · Human Gene Therapy · doi:10.1089/104303401750195935 · Cited by 153
“…which constitutively express the Tet R /VP16 trans -activator from the CMV promoter and also contain the VSV-G envelope gene under the control of a Tet-responsive promoter element, so that in medium containing tetracycline the VSV-G envelope is not expressed (Tet-off system) (Gossen et al ., 1995).”
Magrané, J., Smith, R. C., Walsh, K. X., & Querfurth, H. W. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.4330-03.2004 · Cited by 246
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Hedgehog signaling in pancreas development
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A robust activity marking system for exploring active neuronal ensembles
Sørensen, A. T., Cooper, Y. A., Baratta, M. V., Weng, F., Zhang, Y., Ramamoorthi, K., Fropf, R., LaVerriere, E., Xue, J., Young, A., et al. (2016) · eLife · doi:10.7554/elife.13918 · Cited by 199
“The RAM system: a modular bicistronic AAV vector with optimized temporal control of gene expression We next constructed the RAM system, incorporating PRAM into the doxycycline-dependent Tet-Off system (Gossen et al., 1995).”
MethodKucharzik, T., Hudson, J. T., Lügering, A., Abbas, J., Bettini, M., Lake, J. G., Evans, M. E., Ziegler, T., Merlin, D., Madara, J., et al. (2005) · Gut · doi:10.1136/gut.2004.061168 · Cited by 164
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Itzhaki, J. E., Gilbert, C., & Porter, A. (1997) · Nature Genetics · doi:10.1038/ng0397-258 · Cited by 163
Reglodi, D., Renaud, J., Tamas, A., Tizabi, Y., Socías, S. B., Del-Bel, E., & Raisman-Vozari, R. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.10.004 · Cited by 162
Stringent doxycycline-dependent control of gene activities using an episomal one-vector system
Bornkamm, G., Berens, C., Kuklik-Roos, C., Béchet, J., Laux, G., Bachl, J., Korndoerfer, M., Schlee, M., Hölzel, M., Malamoussi, A., et al. (2005) · Nucleic Acids Research · doi:10.1093/nar/gni137 · Cited by 162
“Two complementary systems have been developed in which the addition of the tetracycline derivative doxycycline (Dox) either switches transcription of a target gene off (tTA or ‘Tet Off’ system) (1) or on (rtTA or ‘Tet On’ system) (5).”
Self-citationWang, H.-Y., Maechler, P., Hagenfeldt, K., & Wollheim, C. (1998) · EMBO Journal · doi:10.1093/emboj/17.22.6701 · Cited by 162
Cholinergic strategies for Alzheimer’s disease
Winkler, J., Thal, L., Gage, F., & Fisher, L. J. (1998) · Journal of molecular medicine · doi:10.1007/s001090050250 · Cited by 162
“A second system that has been recently been described involves the use of a tetracycline (TET)-responsive element to control transgene expression [133, 134].”
BackgroundTemporal control of the Cre recombinase in transgenic mice by a tetracycline responsive promoter.
st-Onge, L., Furth, P., & Gruss, P. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.19.3875 · Cited by 162
Transgenic livestock: Progress and prospects for the future
Wall, R. (1996) · doi:10.1016/0093-691x(95)00355-c · Cited by 162
Simple piggyBac transposon-based mammalian cell expression system for inducible protein production
Li, Z., Michael, I. P., Zhou, D., Nagy, A., & Rini, J. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218620110 · Cited by 152
“The system takes advantage of the ability of the PBase to efficiently mediate the simultaneous integration of multiple DNA fragments (27), a property allowing for the concurrent stable integration of the target protein and the reverse tetracycline transactivator (rtTA) inducer (28) required for doxycycline-mediated ex…”
BackgroundChristen, U., Wolfe, T., Möhrle, U., Hughes, A., Rodrigo, E., Green, E. A., Flavell, R., & von Herrath, M. (2001) · Journal of Immunology · doi:10.4049/jimmunol.166.12.7023 · Cited by 161
“Tet-TNFa mice (8) expressing TNF-a under the control of a Tet-regulated gene transcription system (22) were kindly provided by R.”
MethodEbneth, A., Drewes, G., Mandelkow, E., & Mandelkow, E. (1999) · Cell Motility and the Cytoskeleton · doi:10.1002/(sici)1097-0169(199911)44:3 · Cited by 159
Critical Role for Protein Phosphatase 2A Heterotrimers in Mammalian Cell Survival
Strack, S., Cribbs, J. T., & Gomez, L. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408015200 · Cited by 144
FGF-10 disrupts lung morphogenesis and causes pulmonary adenomas in vivo.
Clark, J., Tichelaar, J., Wert, S., Itoh, N., Perl, A.-K. T., Stahlman, M., & Whitsett, J. (2001) · American Journal of Physiology - Lung cellular and Molecular Physiology · doi:10.1152/ajplung.2001.280.4.l705 · Cited by 160
“In the present study, conditional expression of FGF-10 was achieved utilizing the reverse tetracycline transactivator (rtTA) (11) that is expressed in respiratory epithelial cells under control of either the SP-C or Clara cell secretory protein (CCSP) promoters.”
Methodvan Hengel, J., Vanhoenacker, P., Staes, K., & van Roy, F. (1999) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.96.14.7980 · Cited by 160
Vigna, E., Cavalieri, S., Ailles, L., Geuna, M., Loew, R., Bujard, H., & Naldini, L. (2002) · Molecular Therapy · doi:10.1006/mthe.2002.0542 · Cited by 147
Self-citationDirect regulation of the centrosome duplication cycle by the p53-p21Waf1/Cip1 pathway
Tarapore, P., Horn, H. F., Tokuyama, Y., & Fukasawa, K. (2001) · Oncogene · doi:10.1038/sj.onc.1204424 · Cited by 145
“The plasmids for Tet-inducible expression were constructed in pTRE which uses the rtTA binding site promoter (Gossen et al., 1995).”
MethodGene Therapy Tools for Brain Diseases
Ingusci, S., Verlengia, G., Soukupova, M., Zucchini, S., & Simonato, M. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00724 · Cited by 158
Targeting Expression with Light Using Caged DNA*
Monroe, W., McQuain, M. M., Chang, M. S., Alexander, J., & Haselton, F. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.30.20895 · Cited by 157
Copper ion inducible and repressible promoter systems in yeast.
Labbé, S., & Thiele, D. (1999) · Methods in Enzymology · doi:10.1016/s0076-6879(99)06010-3 · Cited by 157
Bernhard, D., Tinhofer, I., Tonko, M., Hübl, H., Ausserlechner, M., Greil, R., Kofler, R., & Csordas, A. (2000) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400719 · Cited by 156
“C7H2-2C8 is a subclone of the CEM-C7H2 cell line stably transfected with the reverse tetracycline-controlled transcriptional transactivator, rtTA.(57,58) The cell lines C7H2-1E10, 6E2, and 1D2(24) are derivatives of the C7H2-2C8 cell line that are stably”
BackgroundRay, P., Tang, W., Wang, P., Homer, R., Kuhn, C., Flavell, R. A., & Elias, J. A. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119792 · Cited by 137
“mutated tetracycline repressor and the herpes virus VP-16 transactivator (5).”
BackgroundFanning, A., Little, B. P., Rahner, C., Utepbergenov, D., Walther, Z., & Anderson, J. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-08-0764 · Cited by 155
“These constructs were subcloned into either the eukaryotic expression vector pTRE, which is transcriptionally silent in the presence of doxycycline (Gossen et al., 1995), or into the constitutively active expression vector pCB6.”
BackgroundZhu, Z., Ma, B., Homer, R., Zheng, T., & Elias, J. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101512200 · Cited by 135
Sakemura, R. L., Terakura, S., Watanabe, K., Julamanee, J., Takagi, E., Miyao, K., Koyama, D., Goto, T., Hanajiri, R., Nishida, T., et al. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0043 · Cited by 169
A ligand-dependent hammerhead ribozyme switch for controlling mammalian gene expression.
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Berghe, T. V., van Loo, G., Saelens, X., van Gurp, M., Brouckaert, G., Kalai, M., Declercq, W., & Vandenabeele, P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307807200 · Cited by 154
Animal transgenesis: an overview
Sosa, M. A. G., Gasperi, R. D., & Elder, G. A. (2009) · Brain Structure and Function · doi:10.1007/s00429-009-0230-8 · Cited by 146
“For use in transgenic mice the tet repressor was converted into a tet-controlled transcriptional activator (tTA) by fusing the tetR DNA binding domain with the activation domain of the herpes simplex virus VP16 transcriptional activation protein (Gossen et al. 1995) (Fig.”
BackgroundMethodSwitching transgene expression in the brain using an adenoviral tetracycline-regulatable system
Harding, T., Geddes, B., Murphy, D., Knight, D. M., & Uney, J. (1998) · Nature Biotechnology · doi:10.1038/nbt0698-553 · Cited by 152
Yamamoto, M., Wada, N., Kitabatake, Y., Watanabe, D., Anzai, M., Yokoyama, M., Teranishi, Y., & Nakanishi, S. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-17-06759.2003 · Cited by 150
“So that a temporally regulated expression of a transgene in vivo could be achieved, the tetracycline-controlled reverse transactivator (rtTA) system was developed (Gossen et al., 1995).”
BackgroundFavre, D., Blouin, V., Provost, N., Spisek, R., Porrot, F., Bohl, D., Marmé, F., Chérel, Y., Salvetti, A., Hurtrel, B., et al. (2002) · Journal of Virology · doi:10.1128/jvi.76.22.11605-11611.2002 · Cited by 150
Synthetic Biology: Advancing the Design of Diverse Genetic Systems
Wang, Y., Wei, K. Y., & Smolke, C. D. (2013) · Annual Review of Chemical and Biomolecular Engineering · doi:10.1146/annurev-chembioeng-061312-103351 · Cited by 162
“For example, a chimeric protein can be engineered in which a sensor part (rTetR) is fused with a regulator (VP16) that activates transcription (52).”
BackgroundYu, Z., Reichheld, S. E., Savchenko, A., Parkinson, J., & Davidson, A. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.05.062 · Cited by 149
Targeted Sleeping Beauty transposition in human cells.
Ivics, Z., Katzer, A., Stüwe, E. E., Fiedler, D., Knespel, S., & Izsvák, Z. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300169 · Cited by 149
“For this purpose, we concentrated on the TetR-operator system [22].”
MethodIn Vivo Kinetics of mRNA Splicing and Transport in Mammalian Cells
Audibert, A., Weil, D., & Dautry, F. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.19.6706-6718.2002 · Cited by 149
“We therefore generated cell lines in which -globin expression is inducible in the presence of tetracycline by using the reverse tet operator (tet-on system) (15).”
MethodHendrickx, N., Volanti, C., Moens, U. L., Seternes, O. M., de Witte, P. A. M., Vandenheede, J. R., Piette, J. G., & Agostinis, P. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307591200 · Cited by 144
Ray, P., Devaux, Y., Stolz, D., Yarlagadda, M., Watkins, S. C., Lu, Y.-B., Chen, L., Yang, X.-F., & Ray, A. (2003) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1031851100 · Cited by 148
The LDL receptor-related protein LRP6 mediates internalization and lethality of anthrax toxin.
Wei, W.-S., Lu, Q., Chaudry, G., Leppla, S., & Cohen, S. N. (2006) · Cell · doi:10.1016/j.cell.2005.12.045 · Cited by 147
“In these experiments, we used a transactivated tetracycline (Tet)-controlled promoter (Tet-off system) (Gossen and Bujard, 1992; Gossen et al., 1995) on the lentiviral vector pLEST to activate antisense transcription $40,000 human ESTs (Lu et al., 2004) introduced into a population of M2182 human…”
MethodStolze, I. P., Tian, Y.-M., Appelhoff, R. J., Turley, H., Wykoff, C. C., Gleadle, J., & Ratcliffe, P. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406713200 · Cited by 163
Genetic ablation and restoration of the olfactory topographic map.
Gogos, J., Osborne, J., Nemes, A., Mendelsohn, M., & Axel, R. (2000) · Cell · doi:10.1016/s0092-8674(00)00164-1 · Cited by 147
Wang, X., Ryu, D., Houtkooper, R. H., & Auwerx, J. H. (2015) · BioEssays · doi:10.1002/bies.201500071 · Cited by 172
“The Tet-On system is basically operating in the opposite fashion to the Tet-Off system and upon tetracycline binding to the rTA protein it allows it to interact with the TRE and for transcriptional activation to occur [51].”
BackgroundVitale-Cross, L. A., Amornphimoltham, P., Fisher, G. H., Molinolo, A., & Gutkind, J. S. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-2623 · Cited by 133
“9) and cloned into a unique Nhe I site in a pBSKII-derived vector, downstream from the bovine keratin 5 (K5) promoter and upstream from a polyadenylation signal (10).”
BackgroundTransfection of malaria parasites.
Waters, A., Thomas, A., van Dijk, M. V., & Janse, C. (1997) · Methods · doi:10.1006/meth.1997.0506 · Cited by 145
Proinvasion Metastasis Drivers in Early-Stage Melanoma Are Oncogenes
Scott, K. L., Nogueira, C., Heffernan, T. P., van Doorn, R., Dhakal, S., Hanna, J. A., Min, C., Jaskelioff, M., Xiao, Y., Wu, C., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.05.025 · Cited by 144
“The selected melanoma models are: (1) the HRASV12G-driven mouse melanoma model (Tyr-rtTA;TetHRASV12G;INK4A/ARF / , hereafter ‘‘iHRAS*’’), which develops aggressive cutaneous melanomas that do not metastasize (Chin et al., 1997, 1999); and (2) a MET-driven GEM model (Tyr-rtTA;Tet-Met;INK4A/ARF / , hereafter ‘‘iMet’’),…”
Mect1-Maml2 fusion oncogene linked to the aberrant activation of cyclic AMP/CREB regulated genes.
Coxon, A., Rozenblum, E., Park, Y., Joshi, N., Tsurutani, J., Dennis, P., Kirsch, I., & Kaye, F. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1125 · Cited by 144
Rossi, F. M. V., Kringstein, A. M., Spicher, A., Guicherit, O. M., & Blau, H. M. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00070-8 · Cited by 136
“At each intermediate concentration of inducer, an all-or-none rtTAb (Gossen et al., 1995), a chimera of a mutant tetR and the viral response results in a bimodal distribution of expression (two peaks) activator VP16, requires dox to bind tetO, whereas dox prevents with some cells expressing no…”
BackgroundInfluentialLaı́n, S., Midgley, C., Sparks, A., Lane, E. B., & Lane, D. P. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4433 · Cited by 135
Reardon, D., Contessa, J., Mikkelsen, R., Valerie, K., Amir, C., Dent, P., & Schmidt-Ullrich, R. (1999) · Oncogene · doi:10.1038/sj.onc.1202849 · Cited by 143
“…activation of MAPK and JNK1 The MDA-TR15-EGFR-CD533 cell line, a derivative of the parental MDA-MB-231 cell line, expresses dominant negative EGFR-CD533 (Contessa et al., 1999; Redemann et al., 1992) under the control of a two-plasmid Dox-inducible expression system (Gossen et al., 1995).”
BackgroundSilencing and un-silencing of tetracycline-controlled genes in neurons
Zhu, P., Aller, M. I., Baron, U., Cambridge, S., Bausen, M., Herb, J., Sawinski, J., Cetin, A., Osten, P., Nelson, M. L., et al. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000533 · Cited by 136
“For controlling transgenic Tet-responder genes, we used activator mice which express tTA [1,9] and rtTA-M2 [2,28] from the promoter for aCaMKII [9], which is active mainly in principle forebrain neurons.”
An, F., Compitello, N., Horwitz, E., Sramkoski, M., Knudsen, E., & Renne, R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m407435200 · Cited by 140
Kriajevska, M., Fischer-Larsen, M., Moertz, E., Vorm, O., Tulchinsky, E., Grigorian, M., Ambartsumian, N., & Lukanidin, E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110976200 · Cited by 138
Strathdee, C., McLeod, M. R., & Hall, J. R. (1999) · Gene · doi:10.1016/s0378-1119(99)00045-1 · Cited by 138
Vassallo, I., Zinn, P. O., Lai, M., Rajakannu, P., Hamou, M.-F., & Hegi, M. E. (2015) · Oncogene · doi:10.1038/onc.2015.61 · Cited by 136
Genetic Approaches to Investigate the Role of CREB in Neuronal Plasticity and Memory
Barco, Á., & Marie, H. (2011) · Molecular Neurobiology · doi:10.1007/s12035-011-8209-x · Cited by 131
Clusterin Activates Survival through the Phosphatidylinositol 3-Kinase/Akt Pathway
Ammar, H., & Closset, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800403200 · Cited by 129
Lentiviral Vectors for Use in the Central Nervous System
Jakobsson, J., & Lundberg, C. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2005.11.012 · Cited by 132
“A 4amino-acid mutation in the TetR led to a reverse phenotype (rtTA) in which transcription was activated in the presence of tetracycline and vice versa [82].”
BackgroundHsu, W., Shakya, R., & Costantini, F. (2001) · Journal of Cell Biology · doi:10.1083/jcb.200107066 · Cited by 137
“Third, the drug doxycycline (Dox), which can be administered in a temporally specific fashion, induces rtTA to bind to the TRE, turning on the expression of the target gene (Gossen et al., 1995).”
BackgroundMethodInfluentialChemically Regulated Zinc Finger Transcription Factors
Beerli, R. R., Schopfer, U., Dreier, B., & Barbas, C. F. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005108200 · Cited by 135
Classification Framework and Chemical Biology of Tetracycline-Structure-Based Drugs
Fuoco, D. (2012) · Antibiotics · doi:10.3390/antibiotics1010001 · Cited by 141
Bernhard, D., Ausserlechner, M., Tonko, M., Löffler, M., Hartmann, B., Csordas, A., & Kofler, R. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.14.1991 · Cited by 136
“C7H2–2A10 (31) and C7H2–2C8 (32) are subclones of the CEM-C7H2 cell line stably transfected with the tetracycline-controlled transcriptional transactivator, tTA (33), or the reverse tTA, rtTA (34), respectively.”
BackgroundWaxman, A. B., Einarsson, Ó., Seres, T., Knickelbein, R. G., Homer, R., Warshaw, J. B., Johnston, R. B., & Elias, J. A. (1999) · CHEST Journal · doi:10.1378/chest.116.suppl_1.8s · Cited by 72
Bohl, D., Salvetti, A., Moullier, P., & Heard, J. (1998) · Blood · doi:10.1182/blood.v92.5.1512.417k43_1512_1517 · Cited by 136
Wang, H.-Y., & Iynedjian, P. (1997) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.94.9.4372 · Cited by 136
Adeno-Associated Virus Vectors as Therapeutic and Investigational Tools in the Cardiovascular System
Zacchigna, S., Zentilin, L., & Giacca, M. (2014) · Circulation Research · doi:10.1161/circresaha.114.302331 · Cited by 144
Thr207 of claudin-5 is involved in size-selective loosening of the endothelial barrier by cyclic AMP
Soma, T., Chiba, H., Kato‐Mori, Y., Wada, T., Yamashita, T., Kojima, T., & Sawada, N. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.07.012 · Cited by 125
Three-part inventions: intracellular signaling and induced proximity.
Crabtree, G., & Schreiber, S. L. (1996) · TIBS -Trends in Biochemical Sciences. Regular ed · doi:10.1016/s0968-0004(96)20027-1 · Cited by 135
Regulated gene expression systems
Clackson, T. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301120 · Cited by 134
Gonen, H., Bercovich, B., Orian, A., Carrano, A. C., Takizawa, C., Yamanaka, K., Pagano, M., Iwai, K., & Ciechanover, A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.21.14823 · Cited by 133
Secondary mutation maintains the transformed state in BaF3 cells with inducible BCR/ABL expression.
Klucher, K., Lopez, D. V., & Daley, G. (1998) · Blood · doi:10.1182/blood.v91.10.3927.3927_3927_3934 · Cited by 133
Delhaye, S., van Pesch, V., & Michiels, T. (2004) · Journal of Virology · doi:10.1128/jvi.78.8.4357-4362.2004 · Cited by 132
“BALB/3T3 cells expressing rtTA (6), the activator of tetracycline-inducible promoters, were transfected with the NLS-eGFP-expressing plasmid.”
Scotin, a novel p53-inducible proapoptotic protein located in the ER and the nuclear membrane
Bourdon, J., Renzing, J., Robertson, P., Fernandes, K., & Lane, D. P. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200203006 · Cited by 126
“H1299Tetwtp53 was derived from H1299 cells that were stably transfected with a tetracycline-inducible vector encoding for wt human p53 (Gossen et al., 1995).”
BackgroundMethodHOXA10 is a critical regulator for hematopoietic stem cells and erythroid/megakaryocyte development
Magnusson, M., Brun, A. C. M., Miyake, N., Larsson, J. T., Ehinger, M., Björnsson, J. M., Wutz, A., Sigvardsson, M., & Karlsson, S. (2007) · Blood · doi:10.1182/blood-2006-10-054676 · Cited by 130
A novel function of IL-12p40 as a chemotactic molecule for macrophages.
Sang, J.-H., Lee, C.-H., Lee, S., Kim, C., Jang, K. L., Shin, H., & Sung, Y. C. (1999) · Journal of Immunology · doi:10.4049/jimmunol.163.5.2902 · Cited by 130
“Bujard, encodes a neomycin phosphotransferase and carries the regulatory region with human CMV promoter/enhancer and the rtTA-gene (22).”
BackgroundViral Evolution as a Tool to Improve the Tetracycline-regulated Gene Expression System
Das, A. T., Zhou, X., Vink, M., Klaver, B., Verhoef, K., Marzio, G., & Berkhout, B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313895200 · Cited by 129
Tetracycline Antibiotics Impair Mitochondrial Function and Its Experimental Use Confounds Research
Chatzispyrou, I. A., Held, N. M., Mouchiroud, L., Auwerx, J. H., & Houtkooper, R. H. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-1626 · Cited by 148
In vivo gene regulation using tetracycline-regulatable systems
Stieger, K., Belbellaa, B., Guiner, C. L., Moullier, P., & Rolling, F. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2008.12.016 · Cited by 130
“The combination of HSV-1-thymindine kinase (HSV-1-TK) with gancyclovir (GCV) is the most widely used system in cancer gene therapy.”
BackgroundResultInfluentialMice with a “Monoclonal Nose”: Perturbations in an Olfactory Map Impair Odor Discrimination
Fleischmann, A., Shykind, B., Sosulski, D. L., Franks, K. M., Glinka, M. E., Mei, D. F., Sun, Y., Kirkland, J., Mendelsohn, M. M., Albers, M. W., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.046 · Cited by 129
“Expression of the Acetophenone Receptor, M71, in the Vast Majority of Sensory Neurons We have generated transgenic mouse lines bearing the construct tet0-M71-IRES-tau-lacZ in which the odorant receptor M71 and the marker protein tau-lacZ are both under the control of a tet-transactivator (tTA)-responsive promoter, tet…”
BackgroundMethodWu, J., & Lingrel, J. (2004) · Oncogene · doi:10.1038/sj.onc.1207996 · Cited by 128
“Here we stably expressed the KLF2 protein in Jurkat leukemia cells using the tetracycline-inducible system (Gossen et al., 1995) and studied the biological consequence of KLF2 expression with regard to cell proliferation.”
MethodGenetic mouse models for bone studies—Strengths and limitations
Elefteriou, F., & Yang, X. (2011) · Bone · doi:10.1016/j.bone.2011.08.021 · Cited by 125
“The Cre-ERT system [8,9] and the tet-ON/tet-OFF systems [10,11] have been most widely used to provide a temporal control of gene recombination.”
MethodHematopoietic Precursor Cells Transiently Reestablish Permissiveness for XInactivation
Savarese, F., Flahndorfer, K., Jaenisch, R., Busslinger, M., & Wutz, A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00810-06 · Cited by 126
“TX/Y mice were obtained and crossed with R26 mice expressing the tetracycline-responsive transactivator nls-rtTA (18) from the ROSA26 locus (46, 49).”
BackgroundInducible gene expression in mammalian cells and transgenic mice.
Saez, E., No, D., West, A. B., & Evans, R. (1997) · Current Opinion in Biotechnology · doi:10.1016/s0958-1669(97)80037-7 · Cited by 126
Pharmaceutical perspectives of nonviral gene therapy.
Mahato, R. I., Smith, L. C., & Rolland, A. (1999) · Advances in Genetics · doi:10.1016/s0065-2660(08)60152-2 · Cited by 126
Cannon, M., Philpott, N., & Cesarman, E. (2003) · Journal of Virology · doi:10.1128/jvi.77.1.57-67.2003 · Cited by 125
“A single plasmid was designed to incorporate the sequences necessary for tight tetracycline inducibility along with the inverted terminal repeat (ITR) sequences from adeno-associated virus type 2 (AAV-2) to maximize the probability of stable integration (29, 30).”
Muramoto, T., Dearmond, S., Scott, M. R., Telling, G., Cohen, F., & Prusiner, S. (1997) · Nature Medicine · doi:10.1038/nm0797-750 · Cited by 125
Tetracycline-inducible expression systems with reduced basal activity in mammalian cells.
Forster, K., Helbl, V., Lederer, T., Urlinger, S., Wittenburg, N., & Hillen, W. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.2.708 · Cited by 125
Self-citationWu, S., Ying, G., Wu, Q., & Capecchi, M. R. (2008) · Nature Protocols · doi:10.1038/nprot.2008.70 · Cited by 133
“In addition to the loss-of-function and conditional alleles, researchers are also using gene targeting to generate precise point mutations, gain-of-function alleles, tetracycline inducible alleles and other sophisticated alteration”
BackgroundWakabayashi, Y., Inoue, J., Takahashi, Y., Matsuki, A., Kosugi-Okano, H., Shinbo, T., Mishima, Y., Niwa, O., & Kominami, R. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)03069-3 · Cited by 130
Tet B or not tet B: advances in tetracycline-inducible gene expression.
Blau, H. M., & Rossi, F. M. (1999) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.96.3.797 · Cited by 124
Metadata
- Authors
- Gossen, M., Freundlieb, S., Bender, G., Müller, G., Hillen, W., & Bujard, H.
- Affiliations
- Heidelberg University (DE)
- ORCID
- Gossen, Manfred
- Venue
- Science
- Published
- 1995-06-23
- Volume
- 268
- Issue
- 5218
- Pages
- 1766-1769
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2005275397
- Cited by
- 2,488
- References
- 0
- Citations by year
- 2026: 31 · 2025: 43 · 2024: 45 · 2023: 49 · 2022: 55 · 2021: 60 · 2020: 68 · 2019: 52 · 2018: 55 · 2017: 47 · 2016: 52 · 2015: 62 · 2014: 53 · 2013: 67 · 2012: 64
- FWCI
- 48.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- tetracycline, transcriptional activation, Tet repressor, VP16 activation domain, doxycycline, gene expression regulation, transcriptional activator, transgenic animals, gene therapy
- MeSH terms
- Amino Acid Sequence, Doxycycline, HeLa Cells, Humans, Molecular Sequence Data, Operator Regions, Genetic, Recombinant Fusion Proteins, Repressor Proteins, Transfection, Viral Proteins, Transcriptional Activation, Trans-Activators, Genes, Reporter, Simplexvirus
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