文献

J-GLOBAL ID：201902238867026923   整理番号：19A1946746

脊髄小脳性運動失調42のマウスモデルにおける変化したCa_v3.1チャンネル特性を伴う運動失調表現型【JST・京大機械翻訳】

Ataxic phenotype with altered Ca_V3.1 channel property in a mouse model for spinocerebellar ataxia 42

著者 (39件)： Hashiguchi Shunta (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Doi Hiroshi (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Kunii Misako (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Nakamura Yukihiro (Department of Pharmacology, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan) ,  Shimuta Misa (Department of Pharmacology, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan) ,  Suzuki Etsuko (Department of Pharmacology, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan) ,  Koyano Shigeru (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Okubo Masaki (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Kishida Hitaru (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Shiina Masaaki (Department of Biochemistry, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Ogata Kazuhiro (Department of Biochemistry, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Hirashima Fumiko (Department of Rehabilitation Medicine, Flower and Forest Tokyo Hospital, 2-3-6 Nishigahara, Kita-ku, Tokyo 114-0024, Japan) ,  Inoue Yukichi (Department of Neurology, Toyama Prefectural Rehabilitation Hospital and Support Center for Children with Disabilities, 36 Shimoiino, Toyama 931-8517, Japan) ,  Kubota Shun (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Hayashi Noriko (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Nakamura Haruko (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Takahashi Keita (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Katsumoto Atsuko (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Tada Mikiko (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Tanaka Kenichi (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Sasaoka Toshikuni (Department of Comparative and Experimental Medicine, Center for Bioresource-based Researches, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata 951-8585, Japan) ,  Miyatake Satoko (Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Miyake Noriko (Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Saitsu Hirotomo (Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Sato Nozomu (Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-0034, Japan) ,  Ozaki Kokoro (Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-0034, Japan) ,  Ohta Kiyobumi (Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-0034, Japan) ,  Yokota Takanori (Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-0034, Japan) ,  Mizusawa Hidehiro (Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-0034, Japan) ,  Mitsui Jun (Department of Neurology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan) ,  Ishiura Hiroyuki (Department of Neurology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan) ,  Yoshimura Jun (Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan) ,  Morishita Shinichi (Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan) ,  Tsuji Shoji (Department of Neurology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan) ,  Takeuchi Hideyuki (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Ishikawa Kinya (Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-0034, Japan) ,  Matsumoto Naomichi (Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan) ,  Ishikawa Taro (Department of Pharmacology, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan) ,  Tanaka Fumiaki (Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan)
資料名： Neurobiology of Disease  (Neurobiology of Disease)
巻： 130  ページ： Null  発行年： 2019年 
JST資料番号： W1774A  ISSN： 0969-9961  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： オランダ (NLD)  言語： 英語 (EN)

抄録/ポイント： 脊髄小脳失調症42(SCA42)は,最近,CACNA1Gにおけるc.5144G>A(p.Arg1715His)突然変異により引き起こされることが示されている神経変性疾患であり,それはT型電位依存性カルシウムチャンネルCa_V3.1をコードする。ここでは,SCA42の大きな日本人家族について述べた。死後の病理学的検査で,SCA42患者においてユビキチン蓄積を伴わない顕著なPurkinje細胞消失を伴う重度の小脳変性が明らかとなった。この突然変異が失調症状と神経変性を引き起こすかどうかを決定するために,SCA42ファミリーで同定された突然変異に対応するCacna1gにおけるc.5168G>A(p.Arg1723His)突然変異を持つknock インマウスを作成した。ヘテロ接合性およびホモ接合性突然変異体の両方は,11~20週齢から失調性表現型を発達させ,50週齢でPurkinje細胞消失を示した。ホモ接合性knock インマウスにおいて,Purkinje細胞の変性変化と分子層の萎縮性薄化が顕著であった。若いマウスからの急性小脳切片を用いたPurkinje細胞の電気生理学的分析は,点突然変異がCa_V3.1チャンネル活性化の電圧依存性を変化させ,過分極後のリバウンド作用電位を低下させたが,Purkinje細胞へのシナプス伝達の基本的性質には有意な影響を及ぼさなかった。最後に,下オリーブ核におけるニューロンの膜電位の共鳴はknock インマウスで減少し,p.Arg1723His Ca_V3.1変異がPurkinje細胞への上昇する線維シグナリングに影響することを示した。全体として,著者らの研究は,CACNA1Gにおける点突然変異がマウスモデルにおいて失調性表現型とPurkinje細胞変性を引き起こすだけでなく,SCA42の初期段階における電気生理学的異常がPurkinje細胞損失に先行することを示す。Copyright 2019 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： *マウス ,  過分極 ,  *表現型 ,  点突然変異 ,  ヒト ,  プルキンエ細胞 ,  *小脳 ,  *運動失調 ,  突然変異 ,  *チャネル ,  ユビキチン ,  萎縮症 ,  シナプス伝達 ,  *マウスモデル ,  遺伝的変異 ,  *ネズミ亜目 ,  *脳
準シソーラス用語： 変異 ,  神経変性 , 【Automatic Indexing@JST】

著者キーワード (8件)： 小脳 ,  脊髄小脳失調42 ,  CACNA1G ,  ノックインマウス ,  Purkinje細胞 ,  下オリーブ核 ,  神経変性 ,  電気生理学

分類 (2件)： 先天性疾患・奇形一般  (GD03010V) ,  神経の基礎医学  (GN01020W)

タイトルに関連する用語 (5件)： 脊髄小脳性運動失調 ,  マウスモデル ,  チャンネル ,  運動失調 ,  表現型