Development of Mutant Rats Useful for Analysis of Immediate Hypersensitivity

对于立即过敏反应的发展，IgE和肥大细胞/嗜碱性粒细胞是必不可少的。本项目的目的是开发大鼠模型，用于分析立即肝敏感反应。得到了以下结果：1）.我们发现Ws/Ws突变大鼠缺乏肥大细胞。大鼠的Ws基因座编码c-kit受体酪氨酸激酶，突变的Ws等位基因在酪氨酸激酶结构域缺失了12个碱基。c-kit的激酶活性明显受损。虽然Ws突变等位基因最初是在BN菌株中发现的，但在这种遗传背景下，纯合子在子宫内死亡。与BN菌株相比，将Ws突变等位基因引入DA菌株获得了一些纯合子。目前我们正在与日本SLC株式会社合作，尝试获得特定无病原体状态下的DA-Ws/Ws大鼠2)。Ws/Ws大鼠感染巴西尼波圆线虫（Nippostrongylus brasiliensis， NB）后，未出现结缔组织型肥大细胞，黏膜肥大细胞少量出现，嗜碱性粒细胞增加50倍。因此，感染nb的正常（+/+）大鼠可认为是肥大细胞（+）嗜碱性粒细胞（+）；nb感染Ws/Ws大鼠为肥大细胞（-）嗜碱性粒细胞（+）；完整+/+大鼠为肥大细胞（+）嗜碱性细胞（-）；完整的Ws/Ws大鼠成为肥大细胞（-）嗜碱性细胞（-）。3）.我们发现的DA-bg/bg大鼠被证明对肥大细胞功能的研究是有用的。

For development of immediate hypersensitivity reaction, IgE and mast cells/basophils are essential. The purpose of the present project is to develop rat models that are useful for the analysis of the immediate hepersensitivity reaction. The following results were obtained. 1).We found that Ws/Ws mutant rats lacked mast cells. The Ws locus of rats encodes the c-kit receptor tyrosine kinase, and the mutant Ws allele is a deletion of 12 bases at the tyrosine kinase domain. The kinase activity of the c-kit was remarkably impaired by this mutation. Although the Ws mutant allele was first found in the BN strain, homozygotes died in utero in this genetic background. In contrast to the BN strain, some homozygotes were obtained when the Ws mutant allele was introduced into DA strain. Now we are attempting to obtain DA-Ws/Ws rats in the specific pathogen-free condition in the colaboration with Japan SLC Co., Ltd. 2).When Ws/Ws rats were infected with Nippostrongylus brasiliensis (NB), connective tissue-type mast cells did not appear, a small number of mucosal mast sells developed and a 50-fold increase of basophils was observed. Therefore, NB-infected normal (+/+) rats may be considered to be mast cells (+) basophils (+) ; NB-infected Ws/Ws rats to be mast cells (-) basophils (+) ; intact +/+ rats to be mast cells (+) basophils (-) ; intact Ws/Ws rats to be mast cells (-) basophils (-). 3).DA-bg/bg rats which had been found by one of us were demonstrated to be useful for studying functions of mast cells.