Analysis of Germline GLI1 Variation Implicates Hedgehog Signalling in the Regulation of Intestinal Inflammatory Pathways (original) (raw)
Figure 5
Gli1+/lacZ Animals Demonstrate More Severe Intestinal Inflammation than WT Littermates in Response to DSS Treatment
(A, B) WT and Gli1+/lacZ animals demonstrate normal thickness and structure of colonic mucosa in the absence of DSS.
(C) WT animals (n = 4) exhibit mild colonic inflammation but do not develop substantial epithelial or ulcerative inflammatory pathology within 4 d of DSS treatment.
(D) Gli1+/lacZ animals (n = 4) develop significant inflammatory infiltration, epithelial damage, and ulceration within 4 d of DSS treatment.
(E) WT animals (n = 14) demonstrate ulceration following DSS treatment.
(F) Gli1+/lacZ animals develop profound intestinal inflammation in response to 3% DSS treatment, with severe epithelial damage in long stretches of their colonic mucosa (n = 9).
(G) Blinded histological scoring of colonic damage after 6 d of DSS treatment. Standard lengths of tissue from the mid colon and distal descending colon were scored in each animal. Gli1+/lacZ animals (n = 6) have more overall inflammatory foci and more long foci (10+ crypt units affected) than WT animals (n = 6). Each dot represents the number of observed foci in an individual animal; the solid line shows the mean observation in each cohort. Red dots indicate the animals that were analyzed for cytokine expression.
(H) Comprehensive colitis scoring [29] of WT and Gli1+/lacZ animals after 4 and 6 d of DSS treatment. _p_-Values for (G) and (H) calculated by the Student's _t_-test.