Generation of a tightly regulated doxycycline-inducible model for studying mouse intestinal biology
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.
|Keywords||Doxycycline, Intestine, Tet-on, Transgene induction, Transgenic mice, Villin|
|Persistent URL||dx.doi.org/10.1002/dvg.20446, hdl.handle.net/1765/24083|
Roth, S., Franken, P.F., van Veelen, W., Blonden, L., Raghoebir, L., Beverloo, H.B., … Smits, R.. (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