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Development of Mutant Rats Useful for Analysis of Immediate Hypersensitivity

可用于速发型超敏反应分析的突变大鼠的培育

基本信息

批准号：
03558010
负责人：
KITAMURA Yukihiko
金额：
$ 10.62万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03558010/
关键词：
Mast Cell Basophil c-kit receptor IgE receptor Allergy Mast Cell-Deficient Rat Intestinal Parasite 即時型アレルギーベージュラット c-kitレセプター stem cell factor 突然変異ラット即時型アレルギ-c-kit遺伝子レセプタ-・タイロシンカイネ-ス

项目摘要

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.

对于速发型超敏反应的发生，IgE和肥大细胞/嗜碱性粒细胞是必需的。本课题的目的是建立可用于分析速发型过敏反应的大鼠模型。获得了以下结果。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等位基因是酪氨酸激酶结构域的12个碱基的缺失。c-kit的激酶活性被这种突变显著削弱。虽然Ws突变等位基因首先在BN株中发现，但在这种遗传背景下，纯合子在子宫内死亡。与BN株相比，当Ws突变等位基因导入DA株时，获得了一些纯合子。目前，我们正在与日本SLC公司合作，尝试在无特定病原体的条件下获得DA-Ws/Ws大鼠，Ltd. 2）。Ws/Ws大鼠感染巴西尼波圆线虫（NB）后，结缔组织型肥大细胞未出现，出现少量粘膜肥大细胞，嗜碱性粒细胞增加50倍。因此，NB感染的正常（+/+）大鼠可被认为是肥大细胞（+）嗜碱性粒细胞（+）; NB感染的Ws/Ws大鼠可被认为是肥大细胞（-）嗜碱性粒细胞（+）;完整的+/+大鼠可被认为是肥大细胞（+）嗜碱性粒细胞（-）;完整的Ws/Ws大鼠可被认为是肥大细胞（-）嗜碱性粒细胞（-）。3）我们发现的DA-bg/bg大鼠是研究肥大细胞功能的理想动物。