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

Ainsley M. Robinson, Ahmed A. Rahman, Simona E. Carbone, Sarron Randall-Demllo, Rhiannon Filippone, Joel C. Bornstein, Rajaraman Eri, Kulmira Nurgali*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Citations (Scopus)

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. 

Original languageEnglish
Pages (from-to)G85-G102
Number of pages18
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume312
Issue number1
DOIs
Publication statusPublished - Jan 2017
Externally publishedYes

Keywords

  • spontaneous chronic colitis
  • intestinal transit
  • colonic motility
  • Winnie mouse model
  • neuromuscular transmission
  • smooth muscle contractions

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