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Publication : Variability of inducible expression across the hematopoietic system of tetracycline transactivator transgenic mice.

First Author  Takiguchi M Year  2013
Journal  PLoS One Volume  8
Issue  1 Pages  e54009
PubMed ID  23326559 Mgi Jnum  J:195871
Mgi Id  MGI:5486087 Doi  10.1371/journal.pone.0054009
Citation  Takiguchi M, et al. (2013) Variability of inducible expression across the hematopoietic system of tetracycline transactivator transgenic mice. PLoS One 8(1):e54009
abstractText  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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