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Alterations of colonic function in the Winnie mouse model of spontaneous chronic colitis

Citation

Robinson, AM and Rahman, AA and Carbone, SE and Randall-Demllo, S and Filippone, R and Bornstein, JC and Eri, R and Nurgali, K, Alterations of colonic function in the Winnie mouse model of spontaneous chronic colitis, AJP: Gastrointestinal and Liver Physiology, 312, (1) pp. G85-G102. ISSN 1522-1547 (2017) [Refereed Article]

DOI: doi:10.1152/ajpgi.00210.2016

Abstract

The Winnie mouse, carrying a missense mutation in Muc2, is a model for chronic intestinal inflammation demonstrating symptoms closely resembling inflammatory bowel disease (IBD). Alterations to the immune environment, morphological structure, and innervation of Winnie mouse colon have been identified; however, analyses of intestinal transit and colonic functions have not been conducted. In this study, we investigated in vivo intestinal transit in radiographic studies and in vitro motility of the isolated colon in organ bath experiments. We compared neuromuscular transmission using conventional intracellular recording between distal colon of Winnie and C57BL/6 mice and smooth muscle contractions using force displacement transducers. Chronic inflammation in Winnie mice was confirmed by detection of lipocalin-2 in fecal samples over 4 wk and gross morphological damage to the colon. Colonic transit was faster in Winnie mice. Motility was altered including decreased frequency and increased speed of colonic migrating motor complexes and increased occurrence of short and fragmented contractions. The mechanisms underlying colon dysfunctions in Winnie mice included inhibition of excitatory and fast inhibitory junction potentials, diminished smooth muscle responses to cholinergic and nitrergic stimulation, and increased number of α-smooth muscle actin-immunoreactive cells. We conclude that diminished excitatory responses occur both prejunctionally and postjunctionally and reduced inhibitory purinergic responses are potentially a prejunctional event, while diminished nitrergic inhibitory responses are probably due to a postjunction mechanism in the Winnie mouse colon. Many of these changes are similar to disturbed motor functions in IBD patients indicating that the Winnie mouse is a model highly representative of human IBD.

NEW & NOTEWORTHY This is the first study to provide analyses of intestinal transit and whole colon motility in an animal model of spontaneous chronic colitis. We found that cholinergic and purinergic neuromuscular transmission, as well as the smooth muscle cell responses to cholinergic and nitrergic stimulation, is altered in the chronically inflamed Winnie mouse colon. The changes to intestinal transit and colonic function we identified in the Winnie mouse are similar to those seen in inflammatory bowel disease patients.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Gastroenterology and Hepatology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Digestive System Disorders
Author:Randall-Demllo, S (Mr Sarron Randall-Demllo)
Author:Eri, R (Associate Professor Raj Eri)
ID Code:117239
Year Published:2017 (online first 2016)
Deposited By:Health Sciences
Deposited On:2017-06-05
Last Modified:2017-11-01
Downloads:0

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