Extended Data Fig. 8: Effect of Nfkbiz on clonal expansion in a mouse model of chronic DSS-induced colitis.
From: Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis
a, Experimental schedule for induction of colitis in R26LacZ/WTNfkbizWT/WTVil1-creER (control) and R26LacZ/WTNfkbizfl/flVil1-creER (Nfkbiz cKO) mice. Cre-mediated recombination was induced by administration of tamoxifen (TAM), followed by induction of colitis by treatment with DSS. b, e, Images of whole-mount X-gal staining of the large intestine from control (top) and Nfkbiz cKO (bottom) mice after tamoxifen administration without (b) or with (e) subsequent treatment with DSS. c, f, Fraction of LacZ-positive areas in the middle to distal colon before (c) or after (f) induction of colitis with DSS according to genotypes. Two-sided Mann–Whitney U test. d, Density of LacZ-positive areas (number per cm2) having indicated sizes in control and Nfkbiz cKO mice before induction of colitis with DSS. g, Colon length (left) and histological score (right) after chronic DSS-induced colitis for the evaluation of severity of colitis. Two-sided Mann–Whitney U test. h, Relative change in weight of Nfkbiz cKO and control mice during three courses of DSS-induced colitis. Data are shown as mean ± s.d. i, Significant enrichment of NFKBIZ target genes (left) and genes associated with the IL-17 signalling pathway (right) among the downregulated genes in rectum epithelium from Nfkbiz cKO mice compared with control mice four days after the start of treatment with DSS. Data were generated from n = 3 biologically independent mice for both genotypes. Two-sided nominal P values were calculated by GSEA.
