A, Diagrams of the tetO-Shp2CSDA, tetO-EGFRL858R [19] and CCSP-rtTA [25] transgenes of mice used in this study. B, The breeding scheme for production of bitransgenic and tritransgenic mice. C, Tissue samples from brain (Br), lung (Lu), liver (Li), spleen (Sp), kidney (Ki), small intestine (In), and colon (Co) of monotransgenic tetO-Shp2CSDA Line-65 (S65) and Line-669 (S669) mice were analyzed by RT-PCR for the presence of Shp2CSDA mRNA. D, C/Sdn bitransgenic mice from Line-65, Line-389, and Line-669 were fed with regular chow or Dox diet for 4 weeks. Lung tissue samples were analyzed by RT-PCR to examine Shp2CSDA mRNA expression. E, C/S65/EL858R and C/S669/EL858R tritransgenic mice were fed with regular rodent chow or Dox diet for 2 or 4 weeks. Lung tissue samples were analyzed by RT-PCR for mRNA expression or by immunoprecipitation-immunoblotting analysis for the presence of Shp2CSDA protein.