Fig. 1

Mifepristone-inducible liver-specific kras^V12 expression in transgenic zebrafish. (A) Schematic diagram of the mifepristone-inducible LexPR system with separate liver-driver and Ras-effector constructs. The liver-specific expression of EGFP-kras^V12 in double-transgenic fish (driver-effector), harboring both cassettes, is activated in trans by the LexPR activator produced from the liver-driver in the presence of mifepristone (RU486). (B–E) Representative 7-dpf fry from the liver-driver (B), Ras-effector (C) and driver-effector double transgenics (D,E). All fry were incubated with 1 µM mifepristone from 3 dpf. The upper panels show a fluorescent image and the lower panels show histology. The liver-driver fry had induced EGFP expression in the liver and a normal liver histology (B). The Ras-effector fry had mCherry expression in the lens as a transgenic marker but no induced EGFP expression in the liver, and also had a normal liver histology (C). EGFP-kras^V12 expression was induced in driver-effector double-transgenic larvae at 3 dpf, causing the development of an enlarged and hyperplastic liver (D) and some individuals showed invasive EGFP-positive cells as indicated by arrows (E). Dotted areas indicate the liver regions. Scale bars: 50 μm.