We first generated mice with TAM-inducible duct cell specific Kras activation and TGFβR2 deletion by crossing LSL-KrasG12D, Tgfbr2flox/flox, and K19CreERT mice (KT-K19CreERT) based on the frequent alterations of Ras and TGFβ/SMAD signaling pathways in human CCA. Here, TGFBR2 is linked to cholangiocarcinoma.