Development of practically usefull Ws/Ws rat and its utilization

Ws/Ws大鼠是1991年在世界上首次发现的大鼠c-kit基因突变体。c-kit基因编码一种受体酪氨酸激酶（KIT），KIT的配体是干细胞因子（SCF），KIT-SCF系统是肥大细胞和Cajal间质细胞（ICC）发育所必需的。目前，在SLC Japan Co. Ltd.中，具有Ws突变的大鼠的兄弟姐妹篇通过几代相互杂交。Ws/Ws大鼠将在不久的将来稳定可用。我们使用Ws/Ws大鼠进行了几项研究。首先，通过测定幽门内压来检查幽门环的功能。在ICC缺陷的Ws/Ws大鼠中，收缩压没有像在+/+大鼠中观察到的那样延长，并且观察到尖峰样波。在Ws/Ws大鼠中观察到的异常棘波被认为是胆汁反流入胃的原因。第二，肥大细胞在纤维化中的作用进行了研究，使用肥大细胞缺陷的Ws/Ws大鼠。在肺和肝纤维化模型中，Ws/Ws大鼠的纤维化比+/+大鼠更显著，表明纤维化组织中肥大细胞的增加不是纤维化的原因，而是纤维化的结果。第三，我们用Ws/Ws大鼠研究了KIT受体在中枢神经系统中的作用。Morris迷宫实验显示Ws/Ws大鼠空间学习障碍，海马脑片电生理检查显示Ws/Ws大鼠突触增强功能受损。

Ws/Ws rat is only the mutant of rat c-kit gene that we first found in the world in 1991. The c-kit gene encodes a receptor tyrosine kinase, KIT.And the ligand for KIT is stem cell factor, SCF.The KIT-SCF system is essential for development of mast cells and interstitial cell of Cajal(ICC). At present, brothers and sisters of rats that have Ws mutation are crossed each other through several generations in SLC Japan Co.Ltd.Ws/Ws rats will be stably available in near future.We carried out several investigations using Ws/Ws rats. First, the function of pyloric ring was examined by measuring intrapyloric pressure. In ICC-deficient Ws/Ws rats, the contraction pressure did not prolong as observed in +/+ rats, and spike-like waves were noted. The abnormal spike-like waves were considered to be a cause of bile reflux into stomach observed in Ws/Ws rats. Second, the role of mast cells in fibrosis was examined using mast cell-deficient Ws/Ws rats. In both lung and liver fibrosis models, fibrosis in Ws/Ws rats was more prominent than that in +/+ rats, suggesting that the increase of mast cells in fibrotic tissues is not a cause but a result of fibrosis. Third, we examined the role of KIT receptor in central nervous system by using Ws/Ws rats. Morris maze task revealed the impairment of spatial learning and the electrophysiological examination of hippocampal slice showed the impairment of synaptic potentiation in Ws/Ws rats.