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遺伝性皮質性小脳萎縮症SCA6の発現機序の解明と非SCA6の原因遺伝子の同定

遗传性皮质小脑萎缩SCA6表达机制的阐明和非SCA6致病基因的鉴定

基本信息

批准号：
11157208
负责人：
水澤英洋
金额：
$ 0.83万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas (A)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至无数据
项目状态：
已结题

项目摘要

他施設から診断以来のあったものを含め、多数のSCA6症例について、その臨床症状の詳細な解析を行いその臨床症候の特徴を明らかにした。また、ヒト脳におけるα1A-Caチャンネル遺伝子の発現を検討し、mRNAは広く神経系に発現しているものの小脳に圧倒的に多く発現しており、かつそれはとくにプルキンエ細胞に多いことを初めて明らかにし、SCA6がプルキンエ細胞に優位の細胞死を来たし(JNNP,1999)、ほぼ純粋な小脳失調症をきたすことをよく説明できることを示した。さらに、α1A-Caチャンネ蛋白に対する特異抗体を作製して、この蛋白の中枢神経系各部位での発現状況を明らかにするとともに、SCA6ではプルキンエ細胞の細胞質中に特異的封入体ができることを初めて明らかにした(Hum Mol Genet,1999)。培養細胞系を用いた研究では、HEK細胞にCAGリピートが正常および異常に伸長しP型とQ系の∧α1A-Caチャンネル遺伝子を導入し、そのチャンネル機能をパッチクランプ法により検討し初めてP型チャンネルではCAG伸長でCa流入が有意に減少することvセらかにした(J Biol Chem,in press)。現在、さらにノックインマウスの作製を進めている。すでに、我国には臨床・病理所見がSCA6とほぼ同一ながら原因の異なる症例(non-SCA6)が、SCA6とほぼ同様に多数存在することを指摘してきたが、現在候補遺伝子を含め連鎖解析を進めており原因となる遺伝子座を見出し(論文投稿中)、さらに原因遺伝子の同定に向けて研究を進めている。

Since the termination of the clinic, he has reported symptoms, most of the cases of SCA6, and the analysis of bed symptoms. This is the first time that you can see that your cell is dead in the first place (JNNP). You can see that your cell is dead in the first place (JNNP). You can see that your cell is dead in the first place (JNNP). 1999). Please tell me that you are suffering from microaphasia. The specific antibodies against alpha-1A-Ca, alpha-protein, protein, In the culture of cell lines, HEK cells were used to study the growth of normal cells, HEK cells were used to study the growth of normal cells, P-type cells were used to study the growth of cell lines, HEK cells were used to study the growth of cell lines, HEK cells were used to study the growth of normal cells, the cells of P-type cells were used to study the growth of normal cells, the cells of P-type cells were used to study the growth of cell lines, HEK cells were used to study the growth of normal cells, the cells of P-type cells were used to study the growth of normal cells, and the cells of P-type and Q-series were used to study the growth of normal cells. the growth rate of P-type cells was significantly higher than that of normal cells (P-type, low-temperature, low-temperature, At present, we are in the process of making progress. The same cause of disease (non-SCA6) was reported in the Department of Clinical Pathology of the hospital in our country. Most of the patients in the same clinic of SCA6 and SCA6 were found to have the same cause of disease. Now there is a link to analyze the cause of the disease. The cause of the disease has been found in the constellation (submitted in the article), and the cause of the disease is the same as the progress of the study.