title: Alterations of the interstitial cells of Cajal and the microstructure of the gastrointestinal tract in KIT distal kinase mutant mice.
abstract: The development and maintenance of interstitial cells of Cajal (ICC) are closely associated with SCF/KIT signal activity. In this study, we evaluate the distribution of ICC in KIT distal kinase domain mutant mice (Wads) and determine whether the loss-of-function mutations in KIT easily lead to gastrointestinal (GI) disorders. ICC were examined by anti-KIT immunohistochemistry and western blotting. The GI microstructure of wild-type (WT) and Wads mice in normal intestines and incomplete intestinal obstruction was evaluated by hematoxylin and eosin staining. The results in Wads(m/m) mice were as follows. Myenteric ICC were obviously decreased in the stomach and colon and were totally absent in the small intestine. Intramuscular ICC were nearly absent in the stomach and irregularly distributed in the colon. Moreover, the smooth muscle thickness of the small intestine was increased 1.3-fold in Wads(m/m), compared to WT and Wads(m/+) mice and the diameter of the intestinal lumen was also enlarged in Wads(m/m) mice. When constructing an incomplete intestinal obstruction model, the extent of distention involved was greater in Wads mice (1.6-fold in Wads(m/+) mice and 1.8-fold in Wads(m/m) mice vs. WT mice). Meanwhile, the intestinal lumen expansion and decrease in ICC were more pronounced in Wads mice than in WT mice. Our results suggest that the KIT distal kinase domain mutation leads to an ICC loss in a subtype and location-specific pattern in Wads(m/m) mice. The injury of the KIT signaling in mutant mice results in more serious pathological manifestations after being exposed to pathogenic factors.
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, People's Republic of China.
authors.forename: Xiaoshuang
authors.initials: X
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Xue
authors.forename: Qian
authors.initials: Q
authors.lastname: Kang
authors.forename: Haimei
authors.initials: H
authors.lastname: Sun
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.forename: Guoquan
authors.initials: G
authors.lastname: Zhang
authors.forename: Deshan
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000818:Animals; D041981:Gastrointestinal Tract / Q000201:enzymology / Q000473:pathology*; D015870:Gene Expression; D056885:Interstitial Cells of Cajal / Q000201:enzymology / Q000473:pathology*; D007415:Intestinal Obstruction / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
chemical_list: D019009:Proto-Oncogene Proteins c-kit