Casp1^−/− and Pycard^−/− mice are highly susceptible to inflammation-driven colon tumorigenesis. (A) Schematic of the four stage model of inflammation-driven tumor progression using the chemical carcinogen AOM and DSS. (B) Kaplan-Meier plot of WT, Casp1^−/−, and Pycard^−/− mouse survival. (C and D) Weight loss after AOM+DSS challenge. (E) Clinical parameters associated with increased gastrointestinal disease. (F) Inflammation and tumors revealed by in vivo high resolution endoscopy of during week 6 of the recurring colitis-driven tumor model. Asterisks indicate large tumors throughout the distal colons. (G) Colon histopathology scores reveal the severity of inflammation, epithelial defects, crypt atrophy, dysplasia, hyperplasia, and area affected in hematoxylin and eosin–stained sections through the mid and distal colon shown, as in Fig. S3. These scores were summed together to generate a HAI. Data shown are representative of three independent experiments and depict the mean ± SEM. Error bars have been omitted from the weight loss data for clarity of presentation. The symbol # indicates P < 0.05 between the AOM/mock and AOM/DSS-treated WT; * indicates P < 0.05 between the gene-deficient strains and WT. For the survival study: WT AOM/mock, n = 6; Casp1^−/− n = 8; Pycard^−/− n = 9; WT n = 9. For all other datasets: WT AOM, n = 3; WT, n = 9; Pycard^−/−, n = 6; Casp1^−/−, n = 3.