title: Discrepancies between c-Kit positive and Ano1 positive ICC-SMP in the W/Wv and wild-type mouse colon; relationships with motor patterns and calcium transients.
abstract: BACKGROUND
  Interstitial cells of Cajal associated with the submuscular plexus (ICC-SMP) generate omnipresent slow-wave activity in the colon and are associated with prominent motor patterns. Our aim was to investigate colon motor dysfunction in W/W(v) mice in which the ICC are reportedly reduced.
  
  
  METHODS
  Whole organ colon motility was studied using spatio-temporal mapping; immunohistochemical staining was carried out for c-Kit and Ano1; calcium imaging was applied to ICC-SMP.
  
  
  RESULTS
  Discrepancies between Ano1 and c-Kit staining were found in both wild-type and W/W(v) colon. ICC-SMP were reduced to ~50% in the W/W(v) mouse colon according to c-Kit immunohistochemistry, but Ano1 staining indicated a normal network of ICC-SMP. The latter was consistent with rhythmic calcium transients occurring at the submucosal border of the colon in W/W(v) mice, similar to the rhythmic transients in wild-type ICC-SMP. Furthermore, the motor pattern associated with ICC-SMP pacemaking, the so-called 'ripples' were normal in the W/W(v) colon.
  
  
  CONCLUSIONS
  c-Kit is not a reliable marker for quantifying ICC-SMP in the mouse colon. Ano1 staining revealed a normal network of ICC-SMP consistent with the presence of a normal 'ripples' motor pattern. We detected a class of Ano1 positive c-Kit negative cells that do not depend on Kit expression for maintenance, a feature shared with ICC progenitors.
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Xuan-Yu
authors.initials: XY
authors.lastname: Wang
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Chen
authors.forename: Kongling
authors.initials: K
authors.lastname: Li
authors.forename: Yong F
authors.initials: YF
authors.lastname: Zhu
authors.forename: George W J
authors.initials: GW
authors.lastname: Wright
authors.forename: Jan D
authors.initials: JD
authors.lastname: Huizinga
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D020013:Calcium Signaling; D018118:Chloride Channels / Q000378:metabolism*; D003106:Colon / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology*; D056885:Interstitial Cells of Cajal / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*
chemical_list: C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; D018118:Chloride Channels; D019009:Proto-Oncogene Proteins c-kit
keywords: Ano1; ICC associated with submuscular plexus (ICC-SMP); Immunohistochemistry; W/Wv mouse colon; c-Kit; colonic motility; spatio-temporal mapping