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

• Project/Area Number: 23791202
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: OGIWARA Ikuo 独立行政法人理化学研究所, 神経遺伝研究チーム, 研究員 (30373286)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 精神発達障害 / てんかん / ナトリウムチャネル遺伝子 / 興奮性神経細胞 / 脳・神経 / 神経科学 / 脳神経疾患 / 電位依存性ナトリウムチャネル

Research Abstract

Mutations of SCN2A gene encoding voltage-gated sodium channel α2, Nav1.2, have been associated with neurodevelopmental disorders. We here demonstrate that mice with selective SCN2A deletion in forebrain neurons died within postnatal day 2 and developed no apparent behavioral seizures. The results indicate that Nav1.2 in forebrain neurons is essential to survival.

Research Products

• [Journal Article] Mouse with Nav1.1 haploinsufficiency, a model for Dravet syndrome, exhibits lowered sociability and learning impairment. (2013)
  • Author(s): Ito S, Ogiwara I, Yamada K, Miyamoto H, Hensch TK, Osawa M, Yamakawa K.
  • Journal Title: Neurobiology of Disease Volume: 49 Pages: 29-40
  • Peer Reviewed
• [Journal Article] A homozygous mutation of voltage-gated sodium channel β_I gene SCN1B in a patient with Dravet syndrome. (2012)
  • Author(s): Ogiwara I, Nakayama T, Yamagata T, Ohtani H, Mazaki M, Tsuchiya S, Inoue Y, Yamakawa K
  • Journal Title: Epilepsia Volume: 53(12)
  • Peer Reviewed
• [Journal Article] Efficacy of stiripentol in a mouse model of severe myoclonic epilepsy in infancy. (2012)
  • Author(s): Cao D, Ohtani H, Ogiwara I, Ohtani S, Takahashi Y, Yamakawa K, Inoue Y
  • Journal Title: Epilepsia Volume: 53(7) Pages: 1140-1145
  • Peer Reviewed
• [Journal Article] Different degrees of loss of function between GEFS+ and SMEI Na_v1.1 missense mutants at the same residue induced by rescuable folding defects. (2012)
  • Author(s): Sugiura Y, Ogiwara I, Hoshi A, Yamakawa K, Ugawa Y
  • Journal Title: Epilepsia Volume: 53(6)
  • Peer Reviewed
• [Journal Article] A homozygous mutation of voltage-gated sodium channel βI gene SCN1B in a patient with Dravet syndrome. (2012)
  • Author(s): Ogiwara I
  • Journal Title: Epilepsia Volume: 53 Issue: 12
  • DOI: 10.1111/epi.12040
  • Peer Reviewed
• [Journal Article] Efficacy of stiripentol in a mouse model of severe myoclonic epilepsy in infancy (2012)
  • Author(s): Dezhi Cao, Hideyuki Ohtani, Ikuo Ogiwara, Sanae Ohtani, Yukitoshi Takahashi, Kazuhiro Yamakawa, Yushi Inoue
  • Journal Title: Epilepsia Volume: 53 Issue: 7 Pages: 1140-1145
  • DOI: 10.1111/j.1528-1167.2012.03497.x
  • Peer Reviewed
• [Journal Article] Different degrees of loss of function between GEFS+ and SMEI Nav1.1 missense mutants at the same residue induced by rescuable folding defects. (2012)
  • Author(s): Sugiura Y
  • Journal Title: Epilepsia Volume: 53 Issue: 6
  • DOI: 10.1111/j.1528-1167.2012.03467.x
  • Peer Reviewed
• [Journal Article] Different degrees of loss of function between GEFS+ and SMEI Nav1.1 missense mutants at the same residue induced by rescuable folding defects. (2012)
  • Author(s): Sugiura, Y., Ogiwara, I., Hoshi, A., Yamakawa, K., Ugawa Y.
  • Journal Title: Epilepsia Volume: -
  • Peer Reviewed
• [Journal Article] Efficacy of stiripentol in a mouse model of severe myoclonic epilepsy in infancy. (2012)
  • Author(s): Cao, D., Ohtani, H., Ogiwara, I., Ohtani, S., Takahashi, Y., Yamakawa, K., Inoue, Y.
  • Journal Title: Epilepsia Volume: -
  • Peer Reviewed
• [Journal Article] Analysis of pharmacological effects of 2-deoxy glucose in Scn1a mutant mice. (2011)
  • Author(s): Ogiwara I, Mazaki E, Inoue I, Yamakawa K
  • Journal Title: Annual Report of the Japan Epilepsy Research Foundation. Volume: 22 Pages: 25-30
• [Journal Article] Acute encephalopathy in a patient with Dravet syndrome. (2011)
  • Author(s): Tsuji M, Mazaki E, Ogiwara I, Wada T, Iai M, Okumura A, Yamashita S, Yamakawa K, Osaka H
  • Journal Title: Neuropediatrics Volume: 42 Issue: 02 Pages: 78-81
  • DOI: 10.1055/s-0031-1279725
  • Peer Reviewed
• [Presentation] Selective deletion of the Scn1a gene encoding voltage-gated sodium channel α1 in parvalbumin positive cells in mice triggers epileptic seizures (2012)
  • Author(s): Ogiwara I, Miyamoto H, Mazaki E, Tamamaki N, Hensch TK, Yamakawa K
  • Organizer: 第46回日本てんかん学会
  • Place of Presentation: 東京都千代田区
  • Year and Date: 2012-10-11
• [Presentation] 高濃度酸素持続吸入による発作時突然死の予防‐Dravet 症候群マウスモデルを用いた検討 (2012)
  • Author(s): 堀米ゆみ, 榛葉俊一, 飯塚眞喜一, 荻原郁夫, 高橋幸利
  • Organizer: 第46回日本てんかん学会
  • Place of Presentation: 東京都千代田区
  • Year and Date: 2012-10-11
• [Presentation] Deletion of a voltage-gated sodium channel αI, Nav1.1, in parvalbumin-positive interneurons confers epileptic seizures in mice (2012)
  • Author(s): Ogiwara I, Miyamoto H, Mazaki E, Tamamaki N, Hensch TK, Yamakawa K
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2012-09-21
• [Presentation] 電位依存性ナトリウムチャネルα2(Scn2a)遺伝子変異マウスに認められたけいれん感受性の亢進 (2012)
  • Author(s): 荻原郁夫、中山東城、山川和弘
  • Organizer: 第54回日本小児神経学会総会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2012-05-18
• [Presentation] Central and obstructive apnea and cardiac arrhythmia during seizures all play roles in sudden death in a Dravet syndrome mouse model (2012)
  • Author(s): Horigome Y, Iizuka M, Ogiwara I, Shinba T, Takahashi Y
  • Organizer: 10^<th> European congress on epileptology.
  • Place of Presentation: 英国London市
• [Presentation] Deletions of SCN1A 5' genomic region with promoter activity in Dravet syndrome (2011)
  • Author(s): Nakayama T, Ogiwara I, Ito K, Kaneda M, Mazaki E, Osaka H, Ohtani H, Inoue Y, Fujiwara T, Uematsu M, Haginoya K, Tsuchiya S, Yamakawa K
  • Organizer: 2012 American epilepsy society's annual meeting.
  • Place of Presentation: 米国Baltimore市
  • Year and Date: 2011-12-03
• [Presentation] Nav1.1-haploinsufficient mice, a model for Dravet syndrome, exhibit learning impairment and autistic-like behaviors (2011)
  • Author(s): Ogiwara I, Ito S, Yamada K, Yamakawa K
  • Organizer: Neuroscience 2011
  • Place of Presentation: 米国Washington 特別区
  • Year and Date: 2011-11-13
• [Presentation] Dravet 症候群モデルマウスに認められた学習障害ならびに自閉症様行動 (2011)
  • Author(s): 荻原郁夫、伊藤進、山田一之、山川和弘
  • Organizer: 第45回日本てんかん学会
  • Place of Presentation: 新潟県新潟市
  • Year and Date: 2011-10-07
• [Presentation] てんかん患者に見出された電位依存性ナトリウムチャネルβ2(SCN2B)遺伝子のミスセンス (2011)
  • Author(s): 山形哲司, 真崎恵美, 荻原郁夫, 井上有史, 山川和弘
  • Organizer: 変異第45回日本てんかん学会
  • Place of Presentation: 新潟県新潟市
  • Year and Date: 2011-10-06
• [Presentation] Scn1a-GFP BAC transgenic mouse lines showed predominant Nav1.1 expression in parvalbumin-positive interneurons in neocortex and hippocampus (2011)
  • Author(s): Ogiwara I, Mazaki E, Itohara S, Yamakawa K
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2011-09-16
• [Presentation] Nav1.1-haploinsufficient mice, a model for Dravet syndrome, exhibit learning impairment and autistic-like behaviors. (2011)
  • Author(s): Ogiwara, I., Ito, S., Yamada, K., Yamakawa, K.
  • Organizer: Neuroscience 2011
  • Place of Presentation: Washington, D.C., USA
• [Presentation] Dravet症候群モデルマウスに認められた学習障害ならびに自閉症様行動 (2011)
  • Author(s): 荻原郁夫、伊藤進、山田一之、山川和弘
  • Organizer: 第45回日本てんかん学会
  • Place of Presentation: 朱鷺メッセ（新潟）
• [Presentation] Scn1a-GFP BAC transgenic mouse lines showed predominant Nav1.1 expression in parvalbumin-positive interneurons in neocortex and hippocampus. (2011)
  • Author(s): Ogiwara, I., Mazaki, E., Itohara, S., Yamakawa, K.
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] Selective deletion of the Scn1a gene encoding voltage-gated sodium channel α1 in parvalbumin positive cells in mice triggers epileptic seizures.
  • Author(s): Ogiwara I
  • Organizer: 第46回日本てんかん学会
  • Place of Presentation: 東京都千代田区
• [Presentation] Deletion of a voltage-gated sodium channel αI, Nav1.1, in parvalbumin-positive interneurons confers epileptic seizures in mice.
  • Author(s): Ogiwara I
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 愛知県名古屋市
• [Presentation] 電位依存性ナトリウムチャネルα2（Scn2a）遺伝子変異マウスに認められたけいれん感受性の亢進
  • Author(s): 荻原郁夫
  • Organizer: 第54回日本小児神経学会総会
  • Place of Presentation: 北海道札幌市
• [Remarks]
  • URL: http://www.riken.jp/r-world/research/results/2012/120927/index.html
• [Remarks] てんかんモデルマウスで自閉症に似た社会性低下と記憶学習障害を発見
  • URL: http://www.riken.jp/pr/press/2012/20120927_2/