Physiology and Pathophysiology of the Interstitial Cells of Cajal:: From Bench to Bedside IV.: Genetic and animal models of GI motility disorders caused by loss of interstitial cells of Cajal
Physiology and Pathophysiology of the Interstitial Cells of Cajal:: From Bench to Bedside IV.: Genetic and animal models of GI motility disorders caused by loss of interstitial cells of Cajal
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DOI：
10.1152/ajpgi.00362.2001
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发表时间：
2002-05-01
影响因子：
4.5
通讯作者：
Ward, SM
中科院分区：
文献类型：
--
作者：
Sanders, KM;Ördög, T;Ward, SM
一些人类运动障碍已被证明与Cajal （ICC）网络间质细胞的缺失或缺陷有关。由于这些研究的组织样本取自患有严重运动障碍的患者，因此很难确定ICC的丧失是疾病过程的原因还是结果。为了确定运动障碍中ICC丢失的因果关系，使用随着运动障碍发展而ICC丢失的动物模型可能是可行的。已经开发了几种具有ICC网络缺陷的模型，其中包括具有Kit信号通路缺陷的动物（例如，具有Kit受体缺陷的白点突变体；具有Kit配体干细胞因子突变的钢突变体；以及长期使用阻断Kit或下游信号蛋白的试剂治疗的动物）。当Kit信号被阻断时，ICC不会死亡，相反，它们会重新分化为平滑肌样表型。糖尿病动物（NOD/LtJ小鼠）、慢性肠梗阻动物和炎症性肠模型也存在与运动障碍相关的ICC网络缺陷。通过用分子和基因组技术研究这些模型，有可能确定导致ICC丢失的信号，并找到将ICC恢复到功能失调组织的方法。本文讨论了利用动物模型研究失去ICC对运动障碍发展的影响的最新进展。
Several human motility disorders have been shown to be associated with loss or defects in interstitial cells of Cajal (ICC) networks. Because tissue samples for these studies were taken from patients with well-advanced motility problems, it is difficult to determine whether the loss of ICC is a cause or a consequence of the disease process. To establish the cause-and-effect relationship of ICC loss in motility disorders, it may be feasible to use animal models in which ICC are lost as motility dysfunction develops. Several models with defects in ICC networks have been developed, and these include animals with defects in the Kit signaling pathway (e. g., white-spotting mutants that have defects in Kit receptors; steel mutants that have mutations in stem cell factor, the ligand for Kit; and animals that are chronically treated with reagents that block Kit or downstream signaling proteins). ICC do not die when Kit signaling is blocked, rather, they redifferentiate into a smooth muscle-like phenotype. Diabetic animals (NOD/LtJ mice), animals with chronic bowel obstruction, and inflammatory bowel models also have defects in ICC networks that have been associated with motility disorders. By studying these models with molecular and genomic techniques it may be possible to determine the signals that cause loss of ICC and find ways of restoring ICC to dysfunctional tissues. This article discusses recent progress in the utilization of animal models to study the consequences of losing ICC on the development of motility disorders.