Gastroenterology
Volume 138, Issue 3 , Pages 1068-1078.e2 , March 2010

A Model to Study the Phenotypic Changes of Interstitial Cells of Cajal in Gastrointestinal Diseases

  • Seungil Ro

      Affiliations

    • Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada
    • ,
  • Chanjae Park

      Affiliations

    • Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada
    • ,
  • Jingling Jin

      Affiliations

    • Huffington Center on Aging and Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas
    • ,
  • Huili Zheng

      Affiliations

    • Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada
    • ,
  • Peter J. Blair

      Affiliations

    • Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada
    • ,
  • Doug Redelman

      Affiliations

    • Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada
    • ,
  • Sean M. Ward

      Affiliations

    • Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada
    • ,
  • Wei Yan

      Affiliations

    • Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada
    • ,
  • Kenton M. Sanders

      Affiliations

    • Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada
    • Corresponding Author InformationReprint requests Address requests for reprints to: Kenton M. Sanders, PhD, Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557. fax: (775) 784 6903

Received 30 July 2009 ,Accepted 5 November 2009.

References 

  1. Huizinga JD, Thuneberg L, Kluppel M, et al. W/Kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature. 1995;373:347–349
  2. Torihashi S, Yokoi K, Nagaya H, et al. New monoclonal antibody (AIC) identifies interstitial cells of Cajal in the musculature of the mouse gastrointestinal tract. Auto Neurosci. 2004;113:16–23
  3. Farrugia G. Interstitial cells of Cajal in health and disease. Neurogastroenterol Motil. 2008;20:54–63
  4. Ward SM, Burns AJ, Torihashi S, et al. Mutation of the protooncogene C-Kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol London. 1994;480:91–97
  5. Burns AJ, Lomax AEJ, Torihashi S, et al. Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. Proc Natl Acad Sci U S A. 1996;93:12008–12013
  6. Ward SM, Beckett EAH, Wang XY, et al. Interstitial cells of Cajal mediate cholinergic neurotransmission from enteric motor neurons. J Neurosci. 2000;20:1393–1403
  7. Gockel I, Bohl JRE, Eckardt VF, et al. Reduction of interstitial cells of Cajal (ICC) associated with neuronal nitric oxide synthase (n-NOS) in patients with achalasia. Am J Gastroenterol. 2008;103:856–864
  8. Khelif K, De Laet MH, Chaouachi B, et al. Achalasia of the cardia in Allgrove's (triple A) syndrome—histopathologic study of 10 cases. Am J Surg Pathol. 2003;27:667–672
  9. He CL, Soffer EE, Ferris CD, et al. Loss of interstitial cells of Cajal and inhibitory innervation in insulin-dependent diabetes. Gastroenterology. 2001;121:427–434
  10. Ordog T, Takayama I, Cheung WKT, et al. Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis. Diabetes. 2000;49:1731–1739
  11. Zarate N, Mearin F, Wang XY, et al. Severe idiopathic gastroparesis due to neuronal and interstitial cells of Cajal degeneration: pathological findings and management. Gut. 2003;52:966–970
  12. Vanderwinden JM, Liu H, Delaet MH, et al. Study of the interstitial cells of Cajal in infantile hypertrophic pyloric stenosis. Gastroenterology. 1996;111:279–288
  13. Midrio P, Vannucchi MG, Pieri L, et al. Delayed development of interstitial cells of Cajal in the ileum of a human case of gastroschisis. J Cell Mol Med. 2008;12:471–478
  14. Boeckxstaens GE, Rumessen JJ, de Wit L, et al. Abnormal distribution of the interstitial cells of Cajal in an adult patient with pseudo-obstruction and megaduodenum. Am J Gastroenterol. 2002;97:2120–2126
  15. Huizinga JD, Berezin I, Sircar K, et al. Development of interstitial cells of Cajal in a full-term infant without an enteric nervous system. Gastroenterology. 2001;120:561–567
  16. Isozaki K, Hirota S, Miyagawa J, et al. Deficiency of c-kit(+) cells in patients with a myopathic form of chronic idiopathic intestinal pseudo-obstruction. Am J Gastroenterol. 1997;92:332–334
  17. Jain D, Moussa K, Tandon M, et al. Role of interstitial cells of Cajal in motility disorders of the bowel. Am J Gastroenterol. 2003;98:618–624
  18. He CL, Burgart L, Wang LN, et al. Decreased interstitial cell of Cajal volume in patients with slow-transit constipation. Gastroenterology. 2000;118:14–21
  19. Lyford GL, He CL, Soffer E, et al. Pan-colonic decrease in interstitial cells of Cajal in patients with slow transit constipation. Gut. 2002;51:496–501
  20. Wedel T, Spiegler J, Soellner S, et al. Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon. Gastroenterology. 2002;123:1459–1467
  21. Vanderwinden JM, Rumessen JJ, Liu H, et al. Interstitial cells of Cajal in human colon and in Hirschsprung's disease. Gastroenterology. 1996;111:901–910
  22. Ward SM, Gershon MD, Keef K, et al. Interstitial cells of Cajal and electrical activity in ganglionic and aganglionic colons of mice. Am J Physiol Gastrointest Liver Physiol. 2002;283:G445–G456
  23. Wang XY, Zarate N, Soderholm JD, et al. Ultrastructural injury to interstitial cells of Cajal and communication with mast cells in Crohn's disease. Neurogastroenterol Motil. 2007;19:349–364
  24. Porcher C, Baldo M, Henry M, et al. Deficiency of interstitial cells of Cajal in the small intestine of patients with Crohn's disease. Am J Gastroenterol. 2002;97:118–125
  25. Lu G, Qian X, Berezin I, et al. Inflammation modulates in vitro colonic myoelectric and contractile activity and interstitial cells of Cajal. Am J Physiol Gastrointest Liver Physiol. 1997;36:G1233–G1245
  26. Ohlsson B, Veress B, Lindgren S, et al. Enteric ganglioneuritis and abnormal interstitial cells of Cajal: features of inflammatory bowel disease. Inflamm Bowel Dis. 2007;13:721–726
  27. Rumessen JJ. Ultrastructure of interstitial cells of Cajal at the colonic submuscular border in patients with ulcerative colitis. Gastroenterology. 1996;111:1447–1455
  28. Patterson D, Koch K, Abell T, et al. A multicenter placebo-controlled study of domperidone in diabetic gastroparesis. Gastroenterology. 1993;104:A564
  29. Ordog T. Interstitial cells of Cajal in diabetic gastroenteropathy. Neurogastroenterol Motil. 2008;20:8–18
  30. Osoegawa K, Tateno M, Woon PY, et al. Bacterial artificial chromosome libraries for mouse sequencing and functional analysis. Genome Res. 2000;10:116–128
  31. Ro S, Hwang SJ, Ordog T, et al. Adenovirus-based short hairpin RNA vectors containing an eGFP marker and mouse U6, human H1 or human U6 promoter. Bio Techniques. 2005;38:625–627
  32. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987;15:8125–8148
  33. Wellershaus K, Degen J, Deuchars J, et al. A new conditional mouse mutant reveals specific expression and functions of connexin36 in neurons and pancreatic β-cells. Exp Cell Res. 2008;314:997–1012
  34. Ro S, Hwang SJ, Muto M, et al. Anatomic modifications in the enteric nervous system of piebald mice and physiological consequences to colonic motor activity. Am J Physiol Gastrointest Liver Physiol. 2006;290:G710–G718
  35. Shagin DA, Barsova EV, Yanushevich YG, et al. GFP-like proteins as ubiquitous metazoan superfamily: evolution of functional features and structural complexity. Mol Biol Evol. 2004;21:841–850
  36. Karolchik D, Kuhn RM, Baertsch R, et al. The UCSC genome browser database: 2008 update. Nucleic Acids Res. 2008;36:D773–D779
  37. Abe S, Lauby G, Boyer C, et al. Lung cells transplanted to irradiated recipients generate lymphohematopoietic progeny. Am J Respir Cell Mol Biol. 2004;30:491–499
  38. Ingalls AM, Dickie MM, Snell GD. Obese, a new mutation in the house mouse. Obes Res. 1996;4:101
  39. Bernex F, DeSepulveda P, Kress C, et al. Spatial and temporal patterns of c-kit-expressing cells in W-lacZ/+ and W-lacZ/W-lacZ mouse embryos. Development. 1996;122:3023–3033
  40. Cairns LA, Moroni E, Levantini E, et al. Kit regulatory elements required for expression in developing hematopoietic and germ cell lineages. Blood. 2003;102:3954–3962
  41. Berrozpe G, Agosti V, Tucker C, et al. A distant upstream locus control region is critical for expression of the Kit receptor gene in mast cells. Mol Cell Biol. 2006;26:5850–5860
  42. Wouters M, Smans K, Vanderwinden JM. W-ZsGreen/+: a new green fluorescent protein knock-in mouse model for the study of KIT-expressing cells in gut and cerebellum. Physiol Genomics. 2005;22:412–421
  43. Quaye IKE, Toku S, Tanaka T. Sequence requirement for nucleolar localisation of rat ribosomal protein L31. Eur J Cell Biol. 1996;69:151–155
  44. Yamamoto T, Watabe K, Nakahara M, et al. Disturbed gastrointestinal motility and decreased interstitial cells of Cajal in diabetic db/db mice. J Gastroenterol Hepatol. 2008;23:660–667

 Conflicts of interest The authors disclose no conflicts.

 Funding Supported by R37 DK-40569 (to K.M.S.) and P01 DK-41315 (to K.M.S.) from the National Institutes of Health (NIH); the Nevada Genomics Center for sequencing services; the UNR Cytometry Center for cytometric services, supported in part by the Nevada INBRE, P20 RR-016464; Whittemore Peterson Institute for providing the FC500 flow cytometer; and Zeiss LSM510 confocal microscope obtained with support from NIH1 S10 RR16871.

PII: S0016-5085(09)01997-0

doi: 10.1053/j.gastro.2009.11.007

Gastroenterology
Volume 138, Issue 3 , Pages 1068-1078.e2 , March 2010

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