Alterations of the interstitial cells of Cajal and the microstructure of the gastrointestinal tract in KIT distal kinase mutant mice
Alterations of the interstitial cells of Cajal and the microstructure of the gastrointestinal tract in KIT distal kinase mutant mice
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DOI：
10.1007/s00441-013-1737-0
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发表时间：
2013
影响因子：
3.6
通讯作者：
Xiao-shuang Li;H. Xue;Qian Kang;Haimei Sun;Shu Yang;Guo-quan Zhang;De‐shan Zhou
中科院分区：
文献类型：
--
作者：
Xiao-shuang Li;H. Xue;Qian Kang;Haimei Sun;Shu Yang;Guo-quan Zhang;De‐shan Zhou
Cajal间质细胞(ICC)的发育和维持与SCF/KIT信号活性密切相关。在这项研究中，我们评估了ICC在KIT远端激酶域突变小鼠(WADS)中的分布，并确定KIT中的功能缺失突变是否容易导致胃肠道(GI)疾病。用抗KIT免疫组织化学和免疫印迹法检测ICC的表达。用苏木精-伊红染色观察WADS小鼠和野生型(WT)小鼠在正常肠道和不完全性肠梗阻时胃肠道的超微结构。在Wadsm/msm小鼠中的实验结果如下：在胃和结肠，肌间ICC明显减少，在小肠完全消失。肌内ICC在胃内几乎不存在，在结肠内呈不规则分布。Wadsm/m组小鼠小肠平滑肌厚度是WT组和Wadsm/+组的1.3倍，肠腔直径也较WADSM/m组大。在构建不完全性肠梗阻模型时，WADS小鼠所涉及的扩张程度更大(WADSM/+小鼠是WADSM/+小鼠的1.6倍，WADSM/M小鼠是WT小鼠的1.8倍)。同时，WADS小鼠的肠腔扩张和ICC的降低比WT小鼠更为明显。我们的结果表明，KIT远端激酶结构域突变导致了Wadsm/m鼠的一种亚型和位置特异性的ICC缺失。突变小鼠在暴露于致病因子后，KIT信号的损伤会导致更严重的病理表现。
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 Wadsm/mmice 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 Wadsm/m, compared to WT and Wadsm/+mice and the diameter of the intestinal lumen was also enlarged in Wadsm/mmice. When constructing an incomplete intestinal obstruction model, the extent of distention involved was greater in Wads mice (1.6-fold in Wadsm/+mice and 1.8-fold in Wadsm/mmice 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 Wadsm/mmice. The injury of the KIT signaling in mutant mice results in more serious pathological manifestations after being exposed to pathogenic factors.