Characterisation of colonic dysplasia-like epithelial atypia in murine colitis.

aimTo determine if exacerbation of pre-existing chronic colitis in Winnie (

methodsWinnie mice and C57BL6 as a genotype control, were administered 1% w/v dextran sulphate sodium (DSS) orally, followed by drinking water alone in week-long cycles for a total of three cycles. After the third cycle, mice were killed and colonic tissue collected for histological and immunohistochemical evaluation. Inflammation and severity of dysplasia in the colonic mucosa were assessed in H&E sections of the colon. Epithelial cell proliferation was assessed using Ki67 and aberrant β-catenin signalling assessed with enzyme-based immunohistochemistry. Extracted RNA from colonic segments was used for the analysis of gene expression using real-time quantitative PCR. Finally, the distribution of Cxcl5 was visualised using immunohistochemistry.

resultsCompared to controls, Winnie mice exposed to three cycles of DSS displayed inflammation mostly confined to the distal-mid colon with extensive mucosal hyperplasia and regenerative atypia resembling epithelial dysplasia. Dysplasia-like changes were observed in 100% of Winnie mice exposed to DSS, with 55% of these animals displaying changes similar to high-grade dysplasia, whereas high-grade changes were absent in wild-type mice. Occasional penetration of the muscularis mucosae by atypical crypts was observed in 27% of Winnie mice after DSS. Atypical crypts however displayed no evidence of oncogenic nuclear β-catenin accumulation, regardless of histological severity. Expression of

conclusionAlterations to the expression of