Assessment of the piroxicam-incited model of synchronized colitis in T-cell receptor alpha chain-deficient mice

Maximo E Lange ¹, Danisa M Bescucci ¹, Valerie F Boras ²

⁰Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, Alberta, Canada.

Animal Models and Experimental Medicine +

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July 12, 2024

View abstract on PubMed

Summary

Piroxicam treatment induces early, multifocal colitis in T-cell receptor alpha chain (TCRα)-deficient mice. This model shows spatial variability in inflammation, requiring consideration for future colitis research.

Area Of Science

Gastroenterology
Immunology
Preclinical Research

Background

T-cell receptor alpha chain (TCRα)-deficient mice model spontaneous colitis.
Existing models exhibit late-onset and variable inflammation timing.
Piroxicam was previously shown to induce early colitis in TCRα-deficient mice, but lacked detailed characterization.

Purpose Of The Study

To provide an in-depth characterization of piroxicam-induced colitis in TCRα-deficient mice.
To analyze spatial histopathologic changes and inflammatory markers.
To evaluate dexamethasone's efficacy in ameliorating this colitis model.

Main Methods

Induction of colitis in TCRα-deficient mice using piroxicam.
Histopathologic examination of the colon and cecum using Swiss roll technique.
Assessment of inflammatory markers and dexamethasone treatment efficacy.

Main Results

Piroxicam consistently induced time-prescribed, multifocal segmental colitis in the proximal colon and cecum.
Observed histopathologic changes included epithelial hyperplasia, goblet cell loss, leukocyte infiltration, and ulceration.
Dexamethasone demonstrated only partial amelioration of proximal colon inflammation, with significant inter-animal variability noted.

Conclusions

Piroxicam reliably induces multifocal colitis in the proximal colon and cecum of TCRα-deficient mice.
The degree of inflammation is more pronounced in the proximal colon than the cecum.
Spatial and inter-replicate variability in inflammation severity are critical factors for this colitis model.

Keywords:

colon dexamethasone histology induction inflammation knockout