Exacerbated enterocolitis and colitis-associated tumorigenesis upon PAK1 deletion results in loss of goblet cells. (A) Weight curve, DAI, and survival of IL10 KO and DKO mice. Weight gain was similar in IL10 KO and DKO. DKO mice showed higher DAI and a trend toward higher mortality (80% vs 46.15%; P = .054) over the course of the experiment. (B) Length measurement of IL10 KO and DKO colons, DKOs had significantly longer colons (P < .01) compared with IL10 KO mice. (C) Histologic analysis showed significantly higher grades of inflammation (P < .05), more dysplastic lesions (P < .01), and a thicker mucosal layer (P < .05) in DKO compared with IL10 KO mouse colons. The average DAI over time indicated a significant increase in DKO compared with IL10 KO mice (P < .05). Length measurement of the small intestine of IL10 KO and DKO mice did not show significant difference as observed in the DKO colon. (D) Exemplary H&E stains of IL10 KO and DKO colons and periodic acid–Schiff (PAS) staining. DKOs showed a reduction in goblet cells throughout the colon indicating an impaired differentiation. (E) Serum cytokines of IL10 KO and DKO mice were analyzed. IL6 was increased significantly (P < .05) in the serum of DKO mice compared with IL10 KO mice. Other cytokines showed no significant differences. (F) Exemplary colonoscopy pictures of 2 IL10 KO mice with macroscopically normal mucosa and 2 DKO mice with hyperproliferative mucosa. DKO mice showed more signs of inflammation and dysplasia in the distal colon (IL10 KO, n = 12; DKO, n = 8). (G) Nonmetric multidimensional scaling of stool samples indicating different bacterial composition in DKO compared with IL10 KO mice. Composition of the bacterial phylum Proteobacteria showed an increase in the Desulfovibrionaceae family. Independent samples t test, ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001.