Molecular pathology of epilepsy associated with mutations of voltage-gated sodium channel gene

• Project/Area Number: 19790747
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: OGIWARA Ikuo The Institute of Physical and Chemical Research, 神経遺伝研究チーム, 研究員 (30373286)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: てんかん / ナトリウムチャネル遺伝子 / インターニューロン / 脳・神経 / 神経科学 / 脳神経疾患

Research Abstract

電位依存性ナトリウムチャネルα1サブユニット(SCN1A)遺伝子は、乳児重症ミオクロニーてんかん(あるいはDravet症候群)の責任遺伝子である。本研究は、抑制性インターニューロン特異的にSCN1A遺伝子を破壊し、この変異マウスにけいれん発作と突然死を認めた。以上の結果は、乳児重症ミオクロニーてんかんの発病機序がインターニューロンの機能不全とする申請者らの従来の仮説を支持した。

Research Products

• [Journal Article] Patients with a sodium channel alpha 1 gene mutation show wide phenotypic variation (2007)
  • Author(s): Osaka, H., Ogiwara, I., Mazaki, E., Okamura, N., Yamashita, S., Iai, M., Yamada, M., Kurosawa, K., Iwamoto, H., Yasui-Furukori, N., Kaneko, S., Fujiwara, T., Inoue, Y., Yamakawa, K
  • Journal Title: Epilepsy Research 75(1) Pages: 46-51
  • Peer Reviewed
• [Journal Article] Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying anScn1a gene mutation (2007)
  • Author(s): Ogiwara, I., Miyamoto, H., Morita, N., Atapour, N,. Mazaki, E., Inoue, I., Takeuchi, T., Itohara, S., Yanagawa, Y., Obata, K., Furuichi, T., Hensch, T. K., Yamakawa, K
  • Journal Title: Journal of Neuroscience 27(22) Pages: 5903-14
  • Peer Reviewed
• [Journal Article] Patients with a sodium channel alpha 1 gene mutation show wide phenotypic variation. (2007)
  • Author(s): Osaka, H.
  • Journal Title: Epilepsy Research 75 Pages: 46-51
  • Peer Reviewed
• [Journal Article] Navl. 1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scnlagene mntation. (2007)
  • Author(s): Ogiwara, I.
  • Journal Title: Journal of Neuroscience 27 Pages: 5903-14
  • Peer Reviewed
• [Presentation] 電位依存性ナトリウムチャネルα1(SCN1A)遺伝子変異とてんかん (2008)
  • Author(s): 荻原郁夫、山川和弘
  • Organizer: 第50回日本小児神経学会総会
  • Place of Presentation: 東京
• [Presentation] Voltage-gated Na+ channel α1 gene is transcribed from two widely separated promoters (2008)
  • Author(s): 荻原郁夫,伊藤公一,真崎恵美,金田誠,山川和弘
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] 難治性乳幼児てんかんに認められた電位依存性ナトリウムチャネルα2遺伝子変異電位 (2008)
  • Author(s): 荻原郁夫、伊藤公一、小坂仁、真崎恵美、井上育代、四家達彦、藤原建樹、井上有史、金田誠、山川和弘
  • Organizer: 日本人類遺伝学会第53回大会
  • Place of Presentation: 横浜
• [Presentation] 電位依存性ナトリウムチャネルα2遺伝子変異を認めた点頭てんかん1症例 (2008)
  • Author(s): 荻原郁夫、伊藤公一、真崎恵美、井上育代、四家達彦、藤原建樹、井上有史、金田誠、山川和弘
  • Organizer: 第42回日本てんかん学会
  • Place of Presentation: 東京
• [Presentation] Mutation analysis of the voltage-gated sodium channel alpha II gene in patients with early childhood intractable epilepsies (2008)
  • Author(s): Ogiwara, I., Ito, K., Osaka, H., Mazaki, E., Inoue, I., Fujiwara, T., Inoue, Y., Kaneda, M., Yamakawa,K.
  • Organizer: Neuroscience 2008
  • Place of Presentation: Washington, D.C
• [Presentation] Voltage-gated Na^+ channel α1 gene is transcribed from two widely separated promoters (2008)
  • Author(s): 萩原郁夫
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] Mutation analysis of the voltage-gated sodium channel alpha II gene in patients with early childhood intractable epilepsies (2008)
  • Author(s): 萩原郁夫
  • Organizer: Neuroscience 2008
  • Place of Presentation: Washington, D. C.
• [Presentation] Epileptic seizures in mice carrying a premature stop codon in the voltage-gated sodium channel alpha 1 gene: a model for human severe myoclonic epilepsy in infancy (2007)
  • Author(s): Ogiwara, I., Miyamoto, H., Morita, N., Atapour, N., Mazaki, E., Inoue, I., Takeuchi, T., Itohara, S., Yanagawa, Y., Obata, K., Furuichi, T., Hensch, T. K., Yamakawa, K
  • Organizer: 第30回日本神経科学大会サテライトシンポジウム
  • Place of Presentation: 横浜
• [Presentation] てんかんと電位依存性ナトリウムチャネル遺伝子変異 (2007)
  • Author(s): 荻原郁夫、真崎恵美、井上育代、森本昌史、小坂仁、萩野谷和裕、井上有史、藤原建樹、山川和弘
  • Organizer: 日本人類遺伝学会第52回大会
  • Place of Presentation: 東京
• [Presentation] Nav1.1 predominantly localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in Nav1.1-deficient mice (2007)
  • Author(s): 荻原郁夫,宮本浩行,森田規之,アタポアナフィセ,真崎恵美,井上育代,柳川右千夫,小幡邦彦,ヘンシュ K. 貴雄,古市貞一,山川和弘
  • Organizer: 第30回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] 乳児重症ミオクロニーてんかんモデルマウスにおける大脳皮質抑制性神経細胞の異常 (2007)
  • Author(s): 荻原郁夫,森田規之,アタポアナフィセ,宮本浩行,井上育代,真崎恵美,柳川右千夫,小幡邦彦,ヘンシュ貴雄,古市貞一,山川和弘
  • Organizer: 第41回日本てんかん学会
  • Place of Presentation: 福岡
• [Presentation] Nav1.1 predominantly localizes to axons in the developing mouse brain (2007)
  • Author(s): Ogiwara, I., Miyamoto, H., Morita, N., Atapour, N., Mazaki, E., Inoue, I., Itohara, S., Yanagawa, Y., Obata, K., Furuichi, T., Hensch, T.K., Yamakawa, K.
  • Organizer: Neuroscience 2007
  • Place of Presentation: San Diego
• [Presentation] Navl. 1 predominantly localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in Navl. 1-deficient mice (2007)
  • Author(s): Ogiwara, I.
  • Organizer: 第30回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] Navl. 1 predominantly localizes to axons in the developing mouse brain (2007)
  • Author(s): Ogiwara, I.
  • Organizer: Neuroscience 2007
  • Place of Presentation: San Diego
• [Remarks]
  • URL: http://www.riken.jp/r-world/info/release/press/2007/070530/detail.html
• [Remarks]
  • URL: http://www.rikenresearch.riken.jp/japan/research/294/
• [Remarks]
  • URL: http://www.riken.jp/r-world/info/release/press/2007/070530/detail.html
• [Remarks]
  • URL: http://www.rikenresearch.riken.jp/japan/research/294/