Establishment of animal model harboring a homologous mutation ofhuman epilepsy and analysis of genomics"

2008 Fiscal Year Final Research Report

• Project/Area Number: 18300137
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Hirosaki University
• Principal Investigator: UENO Shinya Hirosaki University, 大学院・医学研究科, 教授 (00312158)
• Co-Investigator(Kenkyū-buntansha): ARAKI Kimi 熊本大学, 学内共同利用施設等, 准教授 (90211705) ; OKAMOTO Motohiro 三重大学, 大学院・医学研究科, 教授 (10281916) ; TOMIYAMA Masahiko 弘前大学, 大学院・医学研究科, 准教授 (40311542) ; FUKUZAWA Masashi 弘前大学, 農学生命科学部, 准教授 (10231557) ; MIGITA Keisuke 弘前大学, 大学院・医学研究科, 助教 (10352262) ; YAMADA Junko 弘前大学, 大学院・医学研究科, 助教 (30334965) ; MORIYAMA Tomoko 弘前大学, 大学院・医学研究科, 助教 (90400134)
• Research Collaborator: KANEKO Sunao 弘前大学, 大学院・医学研究科, 教授 (40106852)
• Project Period (FY): 2006 – 2008
• Keywords: 脳・神経 / てんかん / 疾患モデル / 遺伝子改変動物 / イオンチャネル

Research Abstract

ヒト常染色体優性夜間前頭葉てんかん責任遺伝子(nACh receptor 遺伝子変異 : S284L)を導入したラット(S284L-Tg)を作出し、脳波解析、行動解析、電気生理的機能解析の結果、Facevalidity(疾患とモデルの表現型の妥当性)、Construct validity(疾患とモデルのメカニズムの妥当性)、Predictive validity(疾患治療薬がモデルにも有効)の3点をクリアする世界初のてんかんモデルラットであることを示し報告した(J.Neurosci 28 (2008) 12465-12476))。

Research Products

• [Journal Article] Establishment of germline-competentembryonic stem cell lines from the MSM/Msstrain (2009)
  • Author(s): Araki, K., Takeda, N., Yoshiki, A.,Obata, Y., Nakagata, N., Shiroishi, T. Moriwaki, K. and Yamamura, K.
  • Journal Title: Mamm Genome 20 Pages: 14-20
  • Peer Reviewed
• [Journal Article] Rats Harboring S284L Chrna4 MutationShow Attenuation of Synaptic and Extrasynaptic GABAergic Transmission and Exhibit the Nocturnal Frontal LobeEpilepsy Phenotyp J (2008)
  • Author(s): Zhu G, Okada M, Yoshida S, Ueno S, MoriF, Takahara T, Saito R, Miura Y, Kishi A,Tomiyama M, Sato A, Kojima T, Fukuma G,Wakabayashi K, Hase K, Ohno H, Kijima H, Takano Y, Mitsudome A, Kaneko S & Hirose S.
  • Journal Title: Neurosci 28 Pages: 12465-12476
  • Peer Reviewed
• [Journal Article] A new family of transcription factors (2008)
  • Author(s): Yamada Y, Wang HY, Fukuzawa M, Barton GJ, Williams JG
  • Journal Title: Development 135 Pages: 3093-3101
  • Peer Reviewed
• [Journal Article] GABAergicdepolarization of the axon initial segmentin cortical principal neurons is caused bythe Na-K-2Cl cotransporter NKCC1. J. (2008)
  • Author(s): Khirug S, Yamada J, Afzalov R, Voipio J, Khiroug L, Kaila K
  • Journal Title: Neurosci 28 Pages: 4635-4639
  • Peer Reviewed
• [Journal Article] Molecular Basis forthe GABAA Receptor-Mediated TonicInhibition in Rat Somatosensory Cortex (2007)
  • Author(s): Yamada J, Furukawa T, Ueno S, Yamamoto S & Fukuda A.
  • Journal Title: Cereb Cortex 17 Pages: 1782-1787
  • Peer Reviewed
• [Journal Article] Insertion of α7 Nicotinic Receptors atNeocortical Layer V GABAergic Synapses IsInduced by a Benzodiazepine, Midazolam (2007)
  • Author(s): Yamamoto S, Yamada J, Ueno S, Kubota H, Furukawa T, Yamamoto S & Fukuda A.
  • Journal Title: Cereb Cortex 17 Pages: 653-660
  • Peer Reviewed
• [Journal Article] Contribution ofCa2+-dependent protein kinase C in thespinal cord to the development ofmechanical allodynia in diabetic mice (2007)
  • Author(s): Honda K., Koguchi M., Koga K., NakajimaK., Kobayashi F., Migita K., Ogata S.,Hirabara Y. Takano Y.
  • Journal Title: Biol. Pharm. Bull 30 Pages: 930-933
  • Peer Reviewed
• [Journal Article] Carbamazepine prevents breakdown ofneurotransmitter release induced byhyperactivation of ryanodine receptor (2007)
  • Author(s): Yoshida S, Okada M, Zhu G, Kaneko S.
  • Journal Title: Neuropharmacology 52 Pages: 1538-1546
  • Peer Reviewed
• [Journal Article] Effects ofinterleukin-1beta on hippocampalglutamate and GABA releases associatedwith Ca2+-induced Ca2+ releasing systems (2006)
  • Author(s): Gang Zhu, G., Okada, M., Yoshida, S. Mori, F. Ueno, S. , et.al.
  • Journal Title: Epilepsy Res 71 Pages: 107-116
  • Peer Reviewed
• [Presentation] ADNFLEモデルラットにおけるGABA伝達機構の障害 (2009)
  • Author(s): 上野伸哉
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-03-18
• [Presentation] 神経因性疼痛モデルマウスの大脳皮質II/III層錐体細胞におけるシナプス応答 (2009)
  • Author(s): 右田啓介
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-03-17
• [Presentation] PRIP-1 is involved in GABAAreceptor-mediated tonic inhibition inbasolateral (2008)
  • Author(s): Yamada J
  • Organizer: SFN2008
  • Place of Presentation: ワシントンDC(米国)
  • Year and Date: 2008-11-16
• [Presentation] GABAergic depolarization ofthe axon initial segment is caused by NKCC1 in cortical principal neurons (2008)
  • Author(s): Yamada J
  • Organizer: Neuroscience2008
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2008-07-10
• [Presentation] Establishment ofembryonic stem cell lines derived from MSM/Ms strain originated from Mus musculusmolossinus (2008)
  • Author(s): Araki, K, et.al.
  • Organizer: 41st Annual Meeting for the Japanese Society of Developmental Biologists (Jointly sponsored by the International Society of DevelopmentalBiologists)
  • Place of Presentation: 徳島
  • Year and Date: 2008-05-28
• [Presentation] Enhanced GABArelease in the medial globus pallidus of a ratmodel of L-DOPA-induced dyskinesia (2007)
  • Author(s): Tomiyama M, Arai A, Kimura T, Watanabe M, Kawarabayashi T, Shoji M.
  • Organizer: XVII WFN World Congress on Parkinson's Diseaseand Related Disorders
  • Place of Presentation: Amsterdam
  • Year and Date: 20070616-20