Generation of a Tightly Regulated Doxycycline-Inducible Model for Studying Mouse Intestinal Biology

S Roth, Patrick Franken, Wendy Veelen, L Blonden, Lalini Raghoebir, Berna Beverloo, E Drunen, Ernst Kuipers, Robbert Rottier, Riccardo Fodde, R Smits

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16 Citations (Scopus)

Abstract

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 tetO-HIST1H2BJ/GFP model to assess inducibility and tissue-specificity. 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. genesis 47:7-13,2009. (C) 2008 Wiley-Liss, Inc.
Original languageUndefined/Unknown
Pages (from-to)7-13
Number of pages7
JournalGenesis
Volume47
Issue number1
DOIs
Publication statusPublished - 2009

Research programs

  • EMC MGC-02-13-03
  • EMC MGC-02-96-01
  • EMC MM-04-20-01

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