Figure 3. Rap1 CKO mice develop spontaneous colitis with adenoma.

(a) Weight loss of −/− mice. Body weights of f/f or −/− mice (n=10) were presented as percentage of original body weight. Data represent means±s.e.m. *¹P<0.02, *²P<0.01, *³P<0.001 versus the corresponding f/f mice. (b; Left) Representative colon morphology of f/f or −/− mice at 8–12 weeks of age. #1 Shows intussusception in the colon. #2 Shows adenoma between caecum and colon. Scale bar, 1 cm. (Right) Light microscopic assessment of damages of colitis. Data represent means±s.e.m. (n=10 in each group), *P<0.001 versus f/f mice. (c) Histology of intestinal inflammation (upper) and adenoma (lower) in −/− mice. Representative low (× 40) and high (× 200; a,b) magnification histological images of large intestines. Upper a and b represent lymphocyte infiltration and loss of glands, respectively, and lower a and b represent mucosal dysplasia. Scale bars, 200 μm. (d; Upper) Representative cytokine profiles of T cells from the colon LP of −/− mice with colitis (n=5). T cells from the colon LP were subjected to flow cytometry to determine the frequency of T_H1 and T_H17, or T_H1 and T_H2, based on their production of IFN-γ, IL-17 and IL-4. (Lower) Graphs represent the means±s.e.m. of the percentages of IL-17-, IFNγ- or IL-4-producing CD4⁺ cells in the colon. (e) [³H]-thymidine uptake by f/f or −/− CD4⁺ T_N cells. Naive CD4⁺ T cells from f/f or −/− mice were unstimulated (none) or stimulated with anti-CD3, ±anti-CD28. Data represent the means±s.e.m. of three independent experiments.*¹P<0.01, *²P<0.02 versus f/f T cells. (f; Left upper) Percentages of Foxp3⁺ cells (relative to all CD4⁺ T cells) in the mLNs, PPs and colon LP of f/f or −/− mice (n=10) at 9 weeks of age. Data represent means±s.e.m. (Left lower) Representative flow-cytometric profiles of the colon. LP of f/f or −/− mice. (Right) Treg-mediated suppression. Control CD4⁺ T_N cells (T_con) were mixed at the indicated ratios with f/f (●) or −/− (▪) Treg cells (Treg).