Dysregulated behaviors caused by temporally and brain region-specific knockout of CaMKIIα

2011 Fiscal Year Final Research Report

• Project/Area Number: 21300121
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: Fujita Health University
• Principal Investigator: MIYAKAWA Tsuyoshi 藤田保健衛生大学, 総合医科学研究所, 教授 (10301780)
• Co-Investigator(Renkei-kenkyūsha): MATSUO Naoki 京都大学, 白眉センター, 特定准教授 (10508956) ; TAKAO Keizo 自然科学研究機構, 生理学研究所・行動学・心理学的解析, 特任准教授 (80420397) ; TOYAMA Keiko 藤田保健衛生大学, 総合医科学研究所, 助教 (20378722) ; OHIRA Koji 藤田保健衛生大学, 総合医科学研究所, 講師 (80402832)
• Project Period (FY): 2009 – 2011
• Keywords: 網羅的行動テストバッテリー / 未成熟歯状回 / 精神疾患 / コンディショナルノックアウト / 行動異常

Research Abstract

Heterozygous calcium/calmodulin-dependent protein kinase II alpha subunit knockout mice(CaMKIIαHKO mice) have profoundly dysregulated behaviors and impaired neuronal development in the dentate gyrus(DG), which might serve as a promising candidate endophenotype of schizophrenia and other human psychiatric disorders. In the present research project, we established conditional knockout strains of mice, in which CaMKIIα is deleted in specific brain regions, such as dentate gyrus and CA3 in hippocampus. We will subject the conditional KO mice to our comprehensive behavioral test battery to clarify which brain area is responsible for which behavioral abnormalities seen in the CaMKIIαHKO mice.

Research Products

• [Journal Article] M4 muscarinic receptor knockout mice display abnormal social behavior and decreased prepulse inhibition (2012)
  • Author(s): Koshimizu H, Leiter LM, Miyakawa T
  • Journal Title: Mol Brain Volume: Volume 5, 10
  • DOI: DOI:10.1186/1756-6606-5-10
  • Peer Reviewed
• [Journal Article] Comprehensive behavioral analysis of ENU-induced Disc1-Q31L and-L100P mutant mice (2012)
  • Author(s): Shoji H, Toyama K, Takamiya Y, Wakana S, Gondo Y, Miyakawa T
  • Journal Title: BMC Res Notes Volume: Vol.5, No.1
  • DOI: DOI:10.1186/1756-0500-5-108
  • Peer Reviewed
• [Journal Article] Adenomatous polyposis coli heterozygous knockout mice display hypoactivity and age-dependent working memory deficits (2011)
  • Author(s): Koshimizu H, Fukui Y, Takao K, Ohira K, Tanda K, Nakanishi K, Toyama K, Oshima M, Taketo MM, Miyakawa T
  • Journal Title: Front Behav Neurosci Volume: Vol.5 Pages: 85
  • DOI: DOI:10.3389/fnbeh.2011.00085
  • Peer Reviewed
• [Journal Article] Expression of the AMPA Receptor Subunits GluR1 and GluR2 is Associated with Granule Cell Maturation in the Dentate Gyrus (2011)
  • Author(s): Hagihara H, Ohira K, Toyama K, Miyakawa T
  • Journal Title: Front Neurogenesis Volume: Vol.5 Pages: 100
  • DOI: DOI:10.3389/fnins.2011.00100
  • Peer Reviewed
• [Journal Article] Chronic treatment with fluoxetine for more than 6 weeks decreases neurogenesis in the subventricular zone of adult mice (2011)
  • Author(s): Ohira K, Miyakawa T
  • Journal Title: Mol Brain Volume: Vol.4 Pages: 10
  • DOI: doi:10.1186/1756-6606-4-10
  • Peer Reviewed
• [Journal Article] T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice (2011)
  • Author(s): Shoji H, Hagihara H, Takao K, Hattori S, Miyakawa T
  • Journal Title: J Vis Exp Volume: Vol.60 Pages: e3300
  • DOI: DOI:10.3791/3300
  • Peer Reviewed
• [Journal Article] Forebrain-specific constitutively active CaMKKα transgenic mice show deficits in hippocampus-dependent long-term memory (2011)
  • Author(s): Kaitsuka T, Li ST, Nakamura K, Takao K, Miyakawa T, Masayuki Matsushita
  • Journal Title: Neurobiol Learn Mem Volume: Vol.96, No.2 Pages: 238-247
  • DOI: DOI:10.1016/j.nlm.2011.04.017
  • Peer Reviewed
• [Journal Article] P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating (2011)
  • Author(s): Takeuchi H, Iba M, Inoue H, Higuchi M, Takao K, Tsukita K, Karatsu Y, Iwamoto Y, Miyakawa T, Suhara T, Trojanowski JQ, Lee VM, Takahashi R
  • Journal Title: PLoS One Volume: Vol.6, No.6 Pages: e21050
  • DOI: DOI:10.1371/journal.pone.0021050
  • Peer Reviewed
• [Journal Article] Relaxin-3-deficient mice showed slight alteration in anxiety-related behavior (2011)
  • Author(s): Watanabe Y, Tsujimura A, Takao K, Nishi K, Ito Y, Yasuhara Y, Nakatomi Y, Yokoyama C, Fukui K, Miyakawa T, Tanaka M
  • Journal Title: Front Behav Neurosci Volume: Vol.5 Pages: 50
  • DOI: DOI:10.3389/fnbeh.2011.00050
  • Peer Reviewed
• [Journal Article] DIP/WISH deficiency enhances synaptic function and performance in the Barnes maze (2011)
  • Author(s): Asrar S, Kaneko K, Takao K, Negandhi J, Matsui M, Shibasaki K, Miyakawa T, Harrison RV, Jia Z, Salter MW, Tominaga M, Fukumi-Tominaga T
  • Journal Title: Mol Brain Volume: Vol.4 Pages: 39
  • DOI: DOI:10.1186/1756-6606-4-39
  • Peer Reviewed
• [Journal Article] Comprehensive behavioral analysis of calcium/calmodulin-dependent protein kinase IV knockout mice (2010)
  • Author(s): Takao K, Tanda K, Nakamura K, Kasahara J, Nakao K, Katsuki M, Nakanishi K, Yamasaki N, Toyama K, Adachi M, Umeda M, Araki T, Fukunaga K, Kondo H, Sakagami H, Miyakawa T
  • Journal Title: PLoS ONE Volume: Vol.5, No.3 Pages: e9460
  • DOI: doi:10.1371/journal.pone.0009460
  • Peer Reviewed
• [Journal Article] Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells (2009)
  • Author(s): Ohira K, Furuta T, Hioki H, Nakamura KC, Kuramoto E, Tanaka Y, Funatsu N, Shimizu K, Oishi T, Hayashi M, Miyakawa T, Kaneko T, Nakamura S
  • Journal Title: Nature Neurosci Volume: Vol.13, No.2 Pages: 173-179
  • DOI: doi:10.1038/nn.2473
  • Peer Reviewed
• [Journal Article] Dissection of hippocampal dentate gyrus from adult mice (2009)
  • Author(s): Hagihara H, Toyama K, Yamasaki N, Miyakawa T
  • Journal Title: J Vis Exp Volume: Vol.33 Pages: e1543
  • DOI: doi:10.3791/1543
  • Peer Reviewed
• [Journal Article] Inhibition of calpain increases LIS1 expression and partially rescues in vivo phenotypes in a mouse model of lissencephaly (2009)
  • Author(s): Yamada M, Yoshida Y, Mori D, Takitoh T, Kengaku M, Umeshima H, Takao K, Miyakawa T, Sato M, Sorimachi H, Wynshaw-Boris A, Hirotsune S
  • Journal Title: Nature Med Volume: Vol.15, No.10 Pages: 1202-1207
  • DOI: doi:10.1038/nm.2023
  • Peer Reviewed
• [Journal Article] Nardilysin regulates axonal maturation and myelination in the central and peripheral nervous system (2009)
  • Author(s): Ohno M, Hiraoka Y, Matsuoka T, Tomimoto T, Takao K, Miyakawa T, Oshima N, Kiyonari H, Kimura T, Kita T, Nishi E
  • Journal Title: Nature Neurosci Volume: Vol.12, No.12 Pages: 1506-1513
  • DOI: doi:10.1038/nn.2438
  • Peer Reviewed
• [Journal Article] Neural activity changes underlying the working memory deficit in alpha-CaMKII heterozygous knockout mice (2009)
  • Author(s): Matsuo N, Yamasaki N, Ohira K, Takao K, Toyama K, Eguchi M, Yamaguchi S, Miyakawa T
  • Journal Title: Front Behav Neurosci Volume: Vol.3 Pages: 20
  • DOI: doi:10.3389/neuro.08.020.2009
  • Peer Reviewed
• [Journal Article] Mice with altered myelin proteolipid protein gene expression display cognitive deficits accompanied by abnormal neuron glia interactions and decreased conduction velocities (2009)
  • Author(s): Tanaka H, Ma J, Tanaka KF, Takao K, Komada M, Tanda K, Suzuki A, Ishibashi T, Baba H, Isa T, Shigemoto R, Ono K, Miyakawa T, Ikenaka K
  • Journal Title: J Neurosci Volume: Vol.29, No.26 Pages: 8363-71
  • DOI: doi:10.1523/JNEUROSCI.3216-08.2009
  • Peer Reviewed
• [Journal Article] Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice (2009)
  • Author(s): Tanda K, Nishi A, Matsuo N, Nakanishi K, Yamasaki N, Sugimoto T, Toyama K, Takao K, Miyakawa T
  • Journal Title: Mol Brain Volume: Vol.2 Pages: 19
  • DOI: doi:10.1186/1756-6606-2-19
  • Peer Reviewed
• [Journal Article] Comprehensive behavioral phenotyping of ryanodine receptor type3(RyR3) knockout mice : decreased social contact duration in two social interaction tests (2009)
  • Author(s): Matsuo N, Tanda K, Nakanisi K, Yamasaki N, Toyama K, Takao K, Takeshima H, Miyakawa T
  • Journal Title: Front Behav Neurosci Volume: Vol.3 Pages: 3
  • DOI: doi:10.3389/neuro.08.003.2009
  • Peer Reviewed
• [Journal Article] Abnormal behavior in a chromosome-engineered mouse model for human 15q11-13 duplication seen in autism (2009)
  • Author(s): Nakatani J, Tamada K, Hatanaka F, Ise S, Ohta H, Inoue K, Tomonaga S, Watanabe Y, Chung YJ, Banerjee R, Iwamoto K, Kato T, Okazawa M, Yamauchi K, Tanda K, Takao K, Miyakawa T, Bradley A, Takumi T
  • Journal Title: Cell Volume: Vol.137, No.7 Pages: 1235-1246
  • DOI: doi:10.1016/j.cell.2009.04.024
  • Peer Reviewed
• [Journal Article] Detection of an Immature Dentate Gyrus Feature In Human Schizophrenia/Bipolar Patients
  • Author(s): Walton NM, Zhou Y, Kogan JH, Shin R, Webster M, Gross AK, Heusner CL, Chen Q, Miyake S, Tajinda K, Tamura K, Miyakawa T, Matsumoto M
  • Journal Title: Transl Psychiatry Volume: (in press)
  • Peer Reviewed
• [Presentation] Immature dentate gyrus as a candidate endophenotype of psychiatric disorders (2012)
  • Author(s): 宮川剛
  • Organizer: International Neuroscience Frontier symposium(招待講演)
  • Place of Presentation: 西安(中国)
  • Year and Date: 20120322-25
• [Presentation] Bidirectional change of maturation status of dentate gyrus neurons : Relevance to neuropsychiatric disorders (2012)
  • Author(s): 宮川剛
  • Organizer: 14th Mind Brain Science Symposium(招待講演)
  • Place of Presentation: 浜松
  • Year and Date: 20120214-15
• [Presentation] Mice lacking Schnurri-2 displayed cortical abnormalities related to schizophrenia (2011)
  • Author(s): 高雄啓三
  • Organizer: Neuroscience 2011
  • Place of Presentation: ワシントンDC(アメリカ)
  • Year and Date: 20111112-16
• [Presentation] Forebrain-specific calcineurin deficiency causes immaturity of the dentate granule cells in adult mice (2011)
  • Author(s): 萩原英雄
  • Organizer: Neuroscience 2011
  • Place of Presentation: ワシントンDC(アメリカ)
  • Year and Date: 20111112-16
• [Presentation] The SNAP-25-PKC site mutation causes immaturity of the dentate granule cells in adult mice (2011)
  • Author(s): 大平耕司
  • Organizer: Neuroscience 2011
  • Place of Presentation: ワシントンDC(アメリカ)
  • Year and Date: 20111112-16
• [Presentation] Retrospective prediction of behavioral state by transcriptome pattern in the dentate gyrus (2011)
  • Author(s): 宮川剛
  • Organizer: 10th Annual MCCS meeting
  • Place of Presentation: ワシントンDC(アメリカ)
  • Year and Date: 20111110-11
• [Presentation] Immature dentate gyrus as a candidate endophenotype of psychiatric disorders (2011)
  • Author(s): 宮川剛
  • Organizer: 第32回内藤コンファレンス(招待講演)
  • Place of Presentation: 北杜
  • Year and Date: 20111018-21
• [Presentation] Bioifnformatics analyses of immature dentate gyrus, an endophenotype shared by behaviorally abnormal mice (2011)
  • Author(s): 宮川剛
  • Organizer: The 6th International Conference of Neurons and Brain Diseases
  • Place of Presentation: プラハ(チェコ)
  • Year and Date: 20110803-05
• [Presentation] Immature dentate gyrus as a candidate endophenotype of psychiatric disorders (2011)
  • Author(s): 宮川剛
  • Organizer: 10th World Congress of the Biological Psychiatry
  • Place of Presentation: プラハ(チェコ)
  • Year and Date: 20110529-0602
• [Presentation] αCaMKII "immature dentate gyrus" and memory (2011)
  • Author(s): 宮川剛
  • Organizer: 13th Annual Meeting International Behavioural and Neural Genetics Society
  • Place of Presentation: ローマ(イタリア)
  • Year and Date: 20110510-15
• [Presentation] Immature dentate gyrus as a candidate endophenotype of psychiatric disorders (2011)
  • Author(s): 宮川剛
  • Organizer: Cold Spring Harbor Laboratory Meeting
  • Place of Presentation: コールドスプリングハーバー、ニューヨーク(アメリカ)
  • Year and Date: 20110412-16
• [Presentation] Immature dentate gyrus as a candidate endophenotype of psychiatric disorders (2011)
  • Author(s): 宮川剛
  • Organizer: Keystone Symposia on Molecular and Cellular Biology
  • Place of Presentation: タオス、ニューメキシコ(アメリカ)
  • Year and Date: 20110109-14
• [Presentation] 神経機能と精神疾患の関わり～精神疾患の中間表現型候補としての未成熟歯状回～ (2011)
  • Author(s): 宮川剛
  • Organizer: 第27回Wakoワークショップ(招待講演)
  • Place of Presentation: 東京
  • Year and Date: 2011-11-22
• [Presentation] Immature dentate gyrus as a candidate endophenotype of psychiatric disorders (2011)
  • Author(s): 宮川剛
  • Organizer: 神戸大学学術講演第46回シグナル伝達医学グローバルCOE学術講演会(招待講演)
  • Place of Presentation: 神戸
  • Year and Date: 2011-08-08
• [Presentation] Deletion of Schnurri-2 causes abnormal behaviors related to schizophrenia and failure in the maturation of the dentate granule cells in mice (2010)
  • Author(s): 高雄啓三
  • Organizer: Neuroscience 2010
  • Place of Presentation: サンディエゴ、カルフォルニア(アメリカ)
  • Year and Date: 20101113-17
• [Presentation] Immature dentate gyrus as a candidate endophenotype of psychiatric disorders (2010)
  • Author(s): 宮川剛
  • Organizer: 2010 Molecular Cellular Cognition Society
  • Place of Presentation: サンディエゴ、カルフォルニア(アメリカ)
  • Year and Date: 20101111-12
• [Presentation] C57BL6亜系統マウスの行動特性 (2010)
  • Author(s): 高雄啓三
  • Organizer: 第33回日本神経科学大会第53回日本神経化学会大会第20回日本神経回路学会大会
  • Place of Presentation: 神戸コンベンションセンター、神戸
  • Year and Date: 20100902-04
• [Presentation] 海馬歯状回の顆粒細胞におけるTDO2の発現 (2010)
  • Author(s): 大平耕司
  • Organizer: 第33回日本神経科学大会第53回日本神経化学会大会第20回日本神経回路学会大会
  • Place of Presentation: 神戸コンベンションセンター、神戸
  • Year and Date: 20100902-04
• [Presentation] 精神疾患モデルマウスの海馬のプロテオーム解析 (2010)
  • Author(s): 萩原英雄
  • Organizer: 第33回日本神経科学大会第53回日本神経化学会大会第20回日本神経回路学会大会
  • Place of Presentation: 神戸コンベンションセンター、神戸
  • Year and Date: 20100902-04
• [Presentation] 精神疾患の中間表現型としての未成熟歯状回 (2010)
  • Author(s): 宮川剛
  • Organizer: 第33回日本神経科学大会第53回日本神経化学会大会第20回日本神経回路学会大会
  • Place of Presentation: 神戸コンベンションセンター、神戸
  • Year and Date: 20100902-04
• [Presentation] Immature dentate gyrus as a candidate endophenotype of psychiatric disorders (2010)
  • Author(s): 高雄啓三
  • Organizer: 4th European Molecular and Cellular Cognition Society(EMCCS) Satellite Meeting at FENS
  • Place of Presentation: アムステルダム(オランダ)
  • Year and Date: 20100701-02
• [Presentation] Immature dentate gyrus is a common endophenotype among five different mouse models of psychiatric disorders (2010)
  • Author(s): 宮川剛
  • Organizer: From Molecules To Neuronal Disease
  • Place of Presentation: ブリストル(イギリス)
  • Year and Date: 20100629-0701
• [Presentation] Behavioral profiles of three C57BL/6 substrains (2010)
  • Author(s): 高雄啓三
  • Organizer: 12th Annual Meeting International Behavioural and Neural Genetics Society
  • Place of Presentation: ハリファックス、ブリティッシュコロンビア(カナダ)
  • Year and Date: 20100512-16
• [Presentation] Immature dentate gyrus as a potential endophenotype for psychiatric disorders (2010)
  • Author(s): 宮川剛
  • Organizer: 12th Annual Meeting International Behavioural and Neural Genetics Society
  • Place of Presentation: ハリファックス、ブリティッシュコロンビア(カナダ)
  • Year and Date: 20100512-16
• [Presentation] 精神疾患の中間表現型としての未成熟歯状回 (2010)
  • Author(s): 宮川剛
  • Organizer: 第57回中部日本生理学会(招待講演)
  • Place of Presentation: 藤田保健衛生大学、名古屋
  • Year and Date: 2010-10-15
• [Presentation] 精神疾患の中間表現型としての未成熟歯状回 (2009)
  • Author(s): 宮川剛
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20091209-12
• [Presentation] 精神疾患の中間表現型としての未成熟歯状回 (2009)
  • Author(s): 宮川剛
  • Organizer: 第19回日本臨床精神神経薬理学会・第39回日本神経精神薬理学会合同年会
  • Place of Presentation: 京都
  • Year and Date: 20091113-15
• [Presentation] Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice (2009)
  • Author(s): 高雄啓三
  • Organizer: Neuroscience 2009
  • Place of Presentation: シカゴ、イリノイ(アメリカ)
  • Year and Date: 20091017-21
• [Presentation] カルシニューリン抑制因子Zaki-4 Tgマウスの行動解析 (2009)
  • Author(s): 遠山桂子
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 20090916-18
• [Presentation] α-CaMKIIへテロ欠損マウスの海馬遺伝子発現パターン解析 (2009)
  • Author(s): 高雄啓三
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 20090916-18
• [Presentation] 精神疾患の中間表現型としての未成熟歯状回 (2009)
  • Author(s): 宮川剛
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 20090916-18
• [Presentation] Deletion of Schnurri-2 causes abnormal behaviors related to psychiatric disorders and failure in the maturation of the dentate granule cells in mice (2009)
  • Author(s): 高雄啓三
  • Organizer: 第36回国際生理学会世界大会
  • Place of Presentation: 京都
  • Year and Date: 20090728-0801
• [Presentation] Omics analysis of immature dentate gyrus : Possible mechanisms underlying maturation failure of granule cells (2009)
  • Author(s): 宮川剛
  • Organizer: 4th International Conference of Neurons and Brain Disease
  • Place of Presentation: トロント、オンタリオ(カナダ)
  • Year and Date: 20090721-23
• [Book] 「こころ」は遺伝子でどこまで決まるのか (2011)
  • Author(s): 宮川剛
  • Total Pages: 254
  • Publisher: NHK出版
• [Patent(Industrial Property Rights)] 精神病モデル動物の作成方法 (2011)
  • Inventor(s): 大西新、南本敬史、永井裕司、須原哲也、宮川剛、萩原英雄
  • Industrial Property Rights Holder: 独立行政法人放射線医学総合研究所、学校法人藤田学園
  • Industrial Property Number: 特許権、特願PCT/JP2011/50757
  • Filing Date: 2011-01-18
• [Patent(Industrial Property Rights)] うつ病治療のための併用剤 (2011)
  • Inventor(s): 西昭徳、外角直樹、首藤隆秀、黒岩真帆美、宮川剛、小林克典、Paul Greengard
  • Industrial Property Rights Holder: 学校法人久留米大学、学校法人日本医科大学、学校法人藤田学園、The Rockfeller University
  • Industrial Property Number: 特許権、特願61/466, 157
  • Filing Date: 2011-03-22
  • Overseas
• [Patent(Industrial Property Rights)] Gm1遺伝子産物欠損非ヒト動物及びその利用法 (2010)
  • Inventor(s): 高橋康彦、片岡正樹、宮川剛、高雄啓三
  • Industrial Property Rights Holder: 住友化学株式会社
  • Industrial Property Number: 特許権、特願2010-87562
  • Filing Date: 2010-04-06