Generation of a tightly regulated doxycycline-inducible model for studying mouse intestinal biology
Genesis: The Journal of Genetics and Development , Volume 47 - Issue 1 p. 7- 13
To develop a sensitive and inducible system to study intestinal biology, we generated a transgenic mouse model expressing the reverse tetracycline transactivator rtTA2-M2 under control of the 12.4 kb murine Villin promoter. The newly generated Villin-rtTA2-M2 mice were then bred with the previously developed tetOHIST1H2BJ/GFP model to assess inducibility and tissues-pecificity. Expression of the histone H2B-GFP fusion protein was observed exclusively upon doxycycline induction and was uniformly distributed throughout the intestinal epithelium. The Villin-rtTA2-M2 was also found to drive transgene expression in the developing mouse intestine. Furthermore, we could detect transgene expression in the proximal tubules of the kidney and in a population of alleged gastric progenitor cells. By administering different concentrations of doxycycline, we show that the Villin-rtTA2-M2 system drives transgene expression in a dosage-dependent fashion. Thus, we have generated a novel doxycycline-inducible mouse model, providing a valuable tool to study the effect of different gene dosages on intestinal physiology and pathology.
|Doxycycline, Intestine, Tet-on, Transgene induction, Transgenic mice, Villin|
|Genesis: The Journal of Genetics and Development|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Roth, S.G, Franken, P.F, van Veelen, W, Blonden, L, Raghoebir, L, Beverloo, H.B, … Smits, M.J.M. (2009). Generation of a tightly regulated doxycycline-inducible model for studying mouse intestinal biology. Genesis: The Journal of Genetics and Development, 47(1), 7–13. doi:10.1002/dvg.20446