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The TNF ΔARE mouse as a model of intestinal fibrosis.

Authors :
Steiner CA
Koch SD
Evanoff T
Welch N
Kostelecky R
Callahan R
Murphy EM
Hall CHT
Lu S
Weiser-Evans MC
Cartwright IM
Colgan SP
Source :
BioRxiv : the preprint server for biology [bioRxiv] 2023 Jan 14. Date of Electronic Publication: 2023 Jan 14.
Publication Year :
2023

Abstract

Background & Aims: Crohn's disease (CD) is a highly morbid chronic inflammatory disease. The majority of CD patients also develop fibrostenosing complications. Despite this, there are no medical therapies for intestinal fibrosis. This is in part due to lack of high-fidelity biomimetic models to enhance understanding and drug development. There is a need to develop in vivo models of inflammatory bowel disease-related intestinal fibrosis. We sought to determine if the TNF <superscript>ΔARE</superscript> mouse, a model of ileal inflammation, may also develop intestinal fibrosis.<br />Methods: Several clinically relevant outcomes were studied including features of structural fibrosis, histological fibrosis, and gene expression. These include the use of a luminal casting technique we developed, traditional histological outcomes, use of second harmonic imaging, and quantitative PCR. These features were studied in aged TNF <superscript>ΔARE</superscript> mice as well as in cohorts of numerous ages.<br />Results: At ages of 24+ weeks, TNF <superscript>ΔARE</superscript> mice develop structural, histological, and genetic changes of ileal fibrosis. Genetic expression profiles have changes as early as six weeks, followed by histological changes occurring as early as 14-15 weeks, and overt structural fibrosis delayed until after 24 weeks.<br />Discussion: The TNF <superscript>ΔARE</superscript> mouse is a viable and highly tractable model of intestinal fibrosis. This model and the techniques employed can be leveraged for both mechanistic studies and therapeutic development for the treatment of intestinal fibrosis.

Details

Language :
English
Database :
MEDLINE
Journal :
BioRxiv : the preprint server for biology
Accession number :
36712048
Full Text :
https://doi.org/10.1101/2023.01.13.523973