Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice.

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....

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Main Authors: Lukas E Dow, Zeina Nasr, Michael Saborowski, Saya H Ebbesen, Eusebio Manchado, Nilgun Tasdemir, Teresa Lee, Jerry Pelletier, Scott W Lowe
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3990578?pdf=render
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author Lukas E Dow
Zeina Nasr
Michael Saborowski
Saya H Ebbesen
Eusebio Manchado
Nilgun Tasdemir
Teresa Lee
Jerry Pelletier
Scott W Lowe
author_facet Lukas E Dow
Zeina Nasr
Michael Saborowski
Saya H Ebbesen
Eusebio Manchado
Nilgun Tasdemir
Teresa Lee
Jerry Pelletier
Scott W Lowe
author_sort Lukas E Dow
collection DOAJ
description 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.
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spelling doaj.art-13acac9bb382401abf4d9568ca84c4b52022-12-21T22:37:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9523610.1371/journal.pone.0095236Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice.Lukas E DowZeina NasrMichael SaborowskiSaya H EbbesenEusebio ManchadoNilgun TasdemirTeresa LeeJerry PelletierScott W LoweTetracycline 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.http://europepmc.org/articles/PMC3990578?pdf=render
spellingShingle Lukas E Dow
Zeina Nasr
Michael Saborowski
Saya H Ebbesen
Eusebio Manchado
Nilgun Tasdemir
Teresa Lee
Jerry Pelletier
Scott W Lowe
Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice.
PLoS ONE
title Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice.
title_full Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice.
title_fullStr Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice.
title_full_unstemmed Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice.
title_short Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice.
title_sort conditional reverse tet transactivator mouse strains for the efficient induction of tre regulated transgenes in mice
url http://europepmc.org/articles/PMC3990578?pdf=render
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