Variability of inducible expression across the hematopoietic system of tetracycline transactivator transgenic mice
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(Published Version)
Date
2013
Authors
Takiguchi, M.
Dow, L.E.
Prier, J.E.
Carmichael, C.L.
Kile, B.T.
Turner, S.J.
Lowe, S.W.
Huang, D.C.S.
Dickins, R.A.
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Labrecque, N.
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Journal article
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PLoS ONE, 2013; 8(1):e54009-1-e54009-10
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Megumi Takiguchi, Lukas E. Dow, Julia E. Prier, Catherine L. Carmichael, Benjamin T. Kile, Stephen J. Turner, Scott W. Lowe, David C.S. Huang, Ross A. Dickins
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Abstract
The tetracycline (tet)-regulated expression system allows for the inducible overexpression of protein-coding genes, or inducible gene knockdown based on expression of short hairpin RNAs (shRNAs). The system is widely used in mice, however it requires robust expression of a tet transactivator protein (tTA or rtTA) in the cell type of interest. Here we used an in vivo tet-regulated fluorescent reporter approach to characterise inducible gene/shRNA expression across a range of hematopoietic cell types of several commonly used transgenic tet transactivator mouse strains. We find that even in strains where the tet transactivator is expressed from a nominally ubiquitous promoter, the efficiency of tet-regulated expression can be highly variable between hematopoietic lineages and between differentiation stages within a lineage. In some cases tet-regulated reporter expression differs markedly between cells within a discrete, immunophenotypically defined population, suggesting mosaic transactivator expression. A recently developed CAG-rtTA3 transgenic mouse displays intense and efficient reporter expression in most blood cell types, establishing this strain as a highly effective tool for probing hematopoietic development and disease. These findings have important implications for interpreting tet-regulated hematopoietic phenotypes in mice, and identify mouse strains that provide optimal tet-regulated expression in particular hematopoietic progenitor cell types and mature blood lineages.
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© 2013 Takiguchi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.