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PLoS One. 2014 Apr 17;9(4):e95236. doi: 10.1371/journal.pone.0095236. eCollection 2014.

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

Author information

1
Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
2
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
3
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.
4
Department of Biochemistry, McGill University, Montreal, Quebec, Canada; The Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec, Canada.
5
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.

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.

PMID:
24743474
PMCID:
PMC3990578
DOI:
10.1371/journal.pone.0095236
[Indexed for MEDLINE]
Free PMC Article

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