∆122p53 mice present persistent colitis following DSS treatment
|dc.identifier.citation||Quazi, T. (2021). ∆122p53 mice present persistent colitis following DSS treatment (Thesis, Master of Biomedical Sciences). University of Otago. Retrieved from http://hdl.handle.net/10523/12115||en|
|dc.description.abstract||Inflammatory bowel disease (IBD) is a leading health concern in New Zealand as it a lifelong condition that may cycle between periods of remission and relapse, often requiring extensive treatments and medical interventions. The two typical forms of this disease are Crohn’s disease and ulcerative colitis, both involving chronic inflammation colon caused by a dysregulated immune response. How the immune response is regulated in IBD in uncertain. Investigations into cancer using transgenic mice that express Δ122p53, a mimic of the human isoform of the tumour protein 53 gene (Δ133p53) display a proinflammatory phenotype with increased serum cytokine concentrations. To investigate a role for Δ133p53 in IBD, we employed the dextran sulfate sodium (DSS)-induced colitis model using Δ122p53 mice. Mice heterozygous for Δ122p53 and wild-type p53 (Δ122p53), and control mice heterozygous for wild-type p53 and a p53 null allele (p53±) were administered DSS for seven days and euthanised at 0, 7, or 14 days after. Colon tissue was taken and investigated for colitis, recovery, and cytokine production using routine histology and RNAscope assays. Analysis of histology sections show that Δ122p53 mice have about twice as much (20.5% versus 10%, p=0.042) of mucosal colitis when compared to p53± mice, immediately after DSS treatment. The DSS-induced colitis persisted for longer but was able to recover in Δ122p53 compared with p53± mice. Seven-day recovery mice had 15.5% and 5.3% of colon mucosa affected by colitis for Δ122p53 mice and p53± mice (p = 0.002). Fourteen-day recovery had no difference in the amount of mucosa affected by inflammation 1.9% versus 1.7% for Δ122p53 and p53± mice, respectively (p = 0.88). Mucosal mRNA expression of various cytokines was also measured in-situ, using RNAscope® analysis (CCL11, CSF2, IL-6, CCL3, IL12B, and IL12RB1). Only IL-6 mRNA had a significant difference in expression between Δ122p53 and p53± mice, in areas of colitis at 7- and 14-days post DSS treatment. This suggests that once Δ122p53 had recovering mucosal architecture at 14 days, there was still an increased inflammatory response with increased IL-6 production. The findings from this study suggest Δ122p53 increases colitis. Future directions include investigating how Δ122p53 facilitates inflammation in colitis and if Δ133p53 is associated with IBD in patients|
|dc.publisher||University of Otago|
|dc.rights||All items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.|
|dc.title||∆122p53 mice present persistent colitis following DSS treatment|
|thesis.degree.name||Master of Biomedical Sciences|
|thesis.degree.grantor||University of Otago|
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