Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract

Pedro J. Gomez-Pinilla, Simon J. Gibbons, Michael R. Bardsley, Andrea Lorincz, Maria J. Pozo, Pankaj J. Pasricha, Matt Van De Rijn, Robert B. West, Michael G. Sarr, Michael L. Kendrick, Robert R. Cima, Eric Dozois, David Larson, Tamas Ordog, Gianrico Farrugia

Research output: Contribution to journalArticle

237 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume296
Issue number6
DOIs
StatePublished - Jun 2009

Fingerprint

Interstitial Cells of Cajal
Gastrointestinal Tract
Mast Cells
Stomach
Gastrointestinal Stromal Tumors
Antibodies
Confocal Microscopy
Small Intestine
Fluorescent Antibody Technique
Colon
Mucous Membrane

Keywords

  • Chloride channels
  • Gastrointestinal motility
  • Immunofluorescence
  • Kit
  • Mast cells

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract. / Gomez-Pinilla, Pedro J.; Gibbons, Simon J.; Bardsley, Michael R.; Lorincz, Andrea; Pozo, Maria J.; Pasricha, Pankaj J.; Van De Rijn, Matt; West, Robert B.; Sarr, Michael G.; Kendrick, Michael L.; Cima, Robert R.; Dozois, Eric; Larson, David; Ordog, Tamas; Farrugia, Gianrico.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 296, No. 6, 06.2009.

Research output: Contribution to journalArticle

Gomez-Pinilla, Pedro J. ; Gibbons, Simon J. ; Bardsley, Michael R. ; Lorincz, Andrea ; Pozo, Maria J. ; Pasricha, Pankaj J. ; Van De Rijn, Matt ; West, Robert B. ; Sarr, Michael G. ; Kendrick, Michael L. ; Cima, Robert R. ; Dozois, Eric ; Larson, David ; Ordog, Tamas ; Farrugia, Gianrico. / Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2009 ; Vol. 296, No. 6.
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abstract = "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.",
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T1 - Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract

AU - Gomez-Pinilla, Pedro J.

AU - Gibbons, Simon J.

AU - Bardsley, Michael R.

AU - Lorincz, Andrea

AU - Pozo, Maria J.

AU - Pasricha, Pankaj J.

AU - Van De Rijn, Matt

AU - West, Robert B.

AU - Sarr, Michael G.

AU - Kendrick, Michael L.

AU - Cima, Robert R.

AU - Dozois, Eric

AU - Larson, David

AU - Ordog, Tamas

AU - Farrugia, Gianrico

PY - 2009/6

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N2 - 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.

AB - 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.

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KW - Gastrointestinal motility

KW - Immunofluorescence

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