Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract.
Populations of interstitial cells of Cajal (ICC) are altered in several gastrointestinal neuromuscular disorders. ICC are identified typically by ultrastructure and expression of Kit (CD117), a protein that is also expressed on mast cells. No other molecular marker currently exists to independently identify ICC. The expression of ANO1 (DOG1, TMEM16A), a Ca(2+)-activated Cl(-) channel, in gastrointestinal stromal tumors suggests it may be useful as an ICC marker. The aims of this study were therefore to determine the distribution of Ano1 immunoreactivity compared with Kit and to establish whether Ano1 is a reliable marker for human and mouse ICC. Expression of Ano1 in human and mouse stomach, small intestine, and colon was investigated by immunofluorescence labeling using antibodies to Ano1 alone and in combination with antibodies to Kit. Colocalization of immunoreactivity was demonstrated by epifluorescence and confocal microscopy. In the muscularis propria, Ano1 immunoreactivity was restricted to cells with the morphology and distribution of ICC. All Ano1-positive cells in the muscularis propria were also Kit positive. Kit-expressing mast cells were not Ano1 positive. Some non-ICC in the mucosa and submucosa of human tissues were Ano1 positive but Kit negative. A few (3.2%) Ano1-positive cells in the human gastric muscularis propria were labeled weakly for Kit. Ano1 labels all classes of ICC and represents a highly specific marker for studying the distribution of ICC in mouse and human tissues with an advantage over Kit since it does not label mast cells.
Enteric Neuroscience Program, Miles and Shirley Fiterman Center for Digestive Diseases and Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
Pedro J
PJ
Gomez-Pinilla
Simon J
SJ
Gibbons
Michael R
MR
Bardsley
Andrea
A
Lorincz
Maria J
MJ
Pozo
Pankaj J
PJ
Pasricha
Matt
M
Van de Rijn
Robert B
RB
West
Michael G
MG
Sarr
Michael L
ML
Kendrick
Robert R
RR
Cima
Eric J
EJ
Dozois
David W
DW
Larson
Tamas
T
Ordog
Gianrico
G
Farrugia
D000328:Adult; D000818:Animals; D000075369:Anoctamin-1; D000954:Antigens, Surface / Q000032:analysis; D018118:Chloride Channels / Q000032:analysis*; D003106:Colon / Q000737:chemistry / Q000166:cytology; D005260:Female; D005748:Gastric Fundus / Q000737:chemistry / Q000166:cytology; D005753:Gastric Mucosa / Q000737:chemistry / Q000166:cytology; D041981:Gastrointestinal Tract / Q000737:chemistry* / Q000166:cytology*; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000166:cytology; D007421:Intestine, Small / Q000737:chemistry / Q000166:cytology; D007583:Jejunum / Q000737:chemistry / Q000166:cytology; D008297:Male; D008407:Mast Cells / Q000737:chemistry / Q000166:cytology; D008565:Membrane Proteins / Q000032:analysis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D011706:Pyloric Antrum / Q000737:chemistry / Q000166:cytology; D013270:Stomach / Q000737:chemistry / Q000166:cytology; D053802:Tryptases / Q000032:analysis
C476213:ANO1 protein, human; C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; D000954:Antigens, Surface; D018118:Chloride Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D019009:Proto-Oncogene Proteins c-kit; D053802:Tryptases