Abstract
s / Pancreatology 15 (2015) S1eS141 S21 time-specific Cre-activation a Flp-dependent, Tamoxifen-inducible CreERT2 was generated. The influence of mast cells in PDAC development and progression was investigated using mast cell-deficient mice. Results: We could show that transgenic Pdx1-Flp;FSF-KrasG12D mice developed PanIN lesions and PDAC similar to well-established Pdx1Cre;LSL-KrasG12D model. Flp-mediated recombination results in CreERT2 expression selectively in KrasG12D positive pancreatic cells. Tamoxifen treatment allows sequential and site specific genetic manipulation of recombined as shown by conditional activation of reporter genes (eGFP). Depletion of mast cells showed no effect on ADMs and PanIN formation and PDAC development. Implantation experiments also indicated that mast cell deficiency as no effect on tumor formation and its progression. Conclusion: Using this novel dual recombination model we are able to sequentially activate or inactivate genes in the pancreas and to target stromal cells in PDAC formation. By this we show that mast cells are dispensable for PDAC development.
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