title: Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice.
abstract: Tetracycline or doxycycline (dox)-regulated control of genetic elements allows inducible, reversible and tissue specific regulation of gene expression in mice. This approach provides a means to investigate protein function in specific cell lineages and at defined periods of development and disease. Efficient and stable regulation of cDNAs or non-coding elements (e.g. shRNAs) downstream of the tetracycline-regulated element (TRE) requires the robust expression of a tet-transactivator protein, commonly the reverse tet-transactivator, rtTA. Most rtTA strains rely on tissue specific promoters that often do not provide sufficient rtTA levels for optimal inducible expression. Here we describe the generation of two mouse strains that enable Cre-dependent, robust expression of rtTA3, providing tissue-restricted and consistent induction of TRE-controlled transgenes. We show that these transgenic strains can be effectively combined with established mouse models of disease, including both Cre/LoxP-based approaches and non Cre-dependent disease models. The integration of these new tools with established mouse models promises the development of more flexible genetic systems to uncover the mechanisms of development and disease pathogenesis.
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Lukas E
authors.initials: LE
authors.lastname: Dow
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: Zeina
authors.initials: Z
authors.lastname: Nasr
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Saborowski
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America.
authors.forename: Saya H
authors.initials: SH
authors.lastname: Ebbesen
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Eusebio
authors.initials: E
authors.lastname: Manchado
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America.
authors.forename: Nilgun
authors.initials: N
authors.lastname: Tasdemir
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: Teresa
authors.initials: T
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada; The Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec, Canada.
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Lowe
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D019076:Transgenes
chemical_list: D012097:Repressor Proteins; C034811:tetracycline resistance-encoding transposon repressor protein
references.citation: Nucleic Acids Res. 2005 Mar 22;33(5):e51
references.pmid: 15784609
references.citation: Genesis. 2006 Jan;44(1):23-8
references.pmid: 16400644
references.citation: J Biol Chem. 2004 Apr 30;279(18):18776-82
references.pmid: 14761948
references.citation: Cell. 1988 Jul 1;54(1):105-15
references.pmid: 2898299
references.citation: Bioessays. 2011 Sep;33(9):701-10
references.pmid: 21735458
references.citation: Nucleic Acids Res. 1997 Nov 1;25(21):4323-30
references.pmid: 9336464
references.citation: Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5547-51
references.pmid: 1319065
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8615-20
references.pmid: 15941831
references.citation: Cell. 2011 Apr 1;145(1):145-58
references.pmid: 21458673
references.citation: Nat Protoc. 2012 Feb 02;7(2):374-93
references.pmid: 22301776
references.citation: Biochem J. 2009 Mar 15;418(3):567-74
references.pmid: 19143658
references.citation: Cancer Cell. 2003 Dec;4(6):437-50
references.pmid: 14706336
references.citation: Biochem Biophys Res Commun. 1997 Aug 18;237(2):318-24
references.pmid: 9268708
references.citation: Cell. 2012 Mar 16;148(6):1099-109
references.pmid: 22424222
references.citation: Genes Dev. 2014 Jan 1;28(1):85-97
references.pmid: 24395249
references.citation: Cell. 2005 May 6;121(3):465-77
references.pmid: 15882627
references.citation: PLoS One. 2013;8(1):e54009
references.pmid: 23326559
references.citation: Nat Protoc. 2009;4(7):1064-72
references.pmid: 19561589
references.citation: Neurobiol Dis. 2008 Mar;29(3):400-8
references.pmid: 18054242
references.citation: Genes Dev. 2001 Dec 15;15(24):3243-8
references.pmid: 11751630
references.citation: Genes Dev. 2011 Aug 1;25(15):1628-40
references.pmid: 21828272
references.citation: Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7963-8
references.pmid: 10859354