Journal article
DNA-binding of the Tet-transactivator curtails antigen-induced lymphocyte activation in mice
E Ottina, V Peperzak, K Schoeler, E Carrington, R Sgonc, M Pellegrini, S Preston, MJ Herold, A Strasser, A Villunger
Nature Communications | NATURE PORTFOLIO | Published : 2017
Abstract
The Tet-On/Off system for conditional transgene expression constitutes state-of-the-art technology to study gene function by facilitating inducible expression in a timed and reversible manner. Several studies documented the suitability and versatility of this system to trace lymphocyte fate and to conditionally express oncogenes or silence tumour suppressor genes in vivo. Here, we show that expression of the tetracycline/doxycycline-controlled Tet-transactivator, while tolerated well during development and in immunologically unchallenged animals, impairs the expansion of antigen-stimulated T and B cells and thereby curtails adaptive immune responses in vivo. Transactivator-mediated cytotoxic..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We are grateful to K. Rossi, C. Soratroi and I. Gaggl for excellent technical assistance or animal care. We thank R. Dickins, D. Tarlinton, J. Zuber and S. Lowe for mice or reagents. We are grateful to D. Bell for the help with the computational analysis. We thank V. Labi and M. Sochalska for the help with flow cytometric data analysis and cell sorting. This work was supported by the MCBO Doctoral College 'Molecular Cell Biology and Oncology' (W1101) and I-1298 (FOR2036), both funded by the Austrian Science Fund (FWF) and the 'Osterreichische Krebshilfe Branch Tirol'. M.J.H. is supported by the National Health and Medical Research Council, Australia project grant APP1049720.