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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.

SUBMITTER: Dow LE 

PROVIDER: S-EPMC3990578 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Dow Lukas E LE   Nasr Zeina Z   Saborowski Michael M   Ebbesen Saya H SH   Manchado Eusebio E   Tasdemir Nilgun N   Lee Teresa T   Pelletier Jerry J   Lowe Scott W SW  

PloS one 20140417 4


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, com  ...[more]

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