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

2012 Fiscal Year Final Research Report

• 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
• 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

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) Pages: e200-203
  • 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) Pages: e111-e114
  • 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
• [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
  • Year and Date: 20121303
• [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] 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
• [Remarks]
  • URL: http://www.riken.jp/r-world/research/results/2012/120927/index.html