Development of practically usefull Ws/Ws rat and its utilization

实用Ws/Ws大鼠的研制及其利用

• 批准号: 10558121
• 负责人: HIROTA Seiichi
• 金额: $ 8.32万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10558121/
• 关键词: c-kit gene; mutant rats; Ws; intrapyloric pressure; fibrosis; memory; Wsラット; 中枢神経系; 海馬; c-kit レセプター; マスト細胞欠損ラット; マスト細胞; 突然変異ラット; 消化管ストローマ細胞腫; レセプターチロシンキナーゼ; カハール介在細胞; c-kit; 近交系ラット; 受容体チロシンキナーゼ

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.

WS/WS大鼠只是我们在1991年在世界上首次发现的大鼠C-KIT基因的突变体。C-KIT基因编码一种受体酪氨酸激酶，KIT。套件和套件的配体是干细胞因子，SCF。kit-scf系统对于开发了摩根细胞和cajal的固定细胞（ICC）的开发至关重要。目前，在SLC Japan Co.ltd.ws/ws大鼠的几代人之间，大鼠的兄弟姐妹彼此之间的跨越几代人，将在不久的将来稳定使用。我们使用WS/WS大鼠进行了几次调查。首先，通过测量调节内压力检查了幽门环的功能。在ICC缺乏的WS/WS大鼠中，收缩压力并未如 +/ +大鼠中观察到的延长，并注意到尖峰样波。异常的尖峰样波被认为是在WS/WS大鼠中观察到的胆汁反流的原因。其次，使用肥大细胞缺陷的WS/WS大鼠检查了肥大细胞在纤维化中的作用。在肺和肝纤维化模型中，WS/WS大鼠的纤维化比 +/ +大鼠中的纤维化更为突出，这表明纤维化组织中肥大细胞的增加不是原因，而是纤维化的结果。第三，我们通过使用WS/WS大鼠检查了试剂盒受体在中枢神经系统中的作用。莫里斯迷宫的任务显示了空间学习的损害，海马切片的电生理检查显示了WS/WS大鼠突触增强的损害。

项目成果

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Isozaki K 等人：“家族性胃肠道间质瘤中 c-kit 基因激酶结构域的种系激活突变。”Am J Pathol.. 157. 1581-1585 (2000)

Tsujimura Y,Kitamura Y et al.: "Activating mutation in the catalytic domain of c-kit elicts hematopoietic transformation"Blood. 93. 1319-1329 (1999)

Tsujimura Y、Kitamura Y 等人：“激活 c-kit 催化结构域中的突变引发造血转化”血液。

Hirota S,Kitamura Y,et al: "Gain-of-function mutations of c-kit in human gastro-intestinal stromal tumors" Sience. 279. 577-580 (1998)

Hirota S、Kitamura Y 等人：“人类胃肠道间质瘤中 c-kit 的功能获得突变”Sience。

Hirota S: "Gain-of-function mutation at extracellular domain of KIT in gastrointestinal stromal tumors."J Pathol. (in press). (2001)

Hirota S：“胃肠道间质瘤中 KIT 胞外域的功能获得突变。”J Pathol。

Taniguchi M, et al: "Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors."Cancer Res.. 59. 4297-4300 (1999)

Taniguchi M 等人：“c-kit 突变对胃肠道间质瘤预后的影响。”Cancer Res.. 59. 4297-4300 (1999)