Behavioral and functional analysis of Shn2 gene using site-and time-specific gene targeting technique

2011 Fiscal Year Final Research Report

• Project/Area Number: 22700338
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neuroscience in general
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: TAKAO Keizo 生理学研究所, 行動・代謝分子解析センター, 特任准教授 (80420397)
• Project Period (FY): 2010 – 2011
• Keywords: 網羅的行動解析 / 歯状回 / 統合失調症

Research Abstract

Site specific Shn2 gene knockout mice can be obtained by crossing floxed Shn2 mice with mice expressing Cre recombinase site-speficically. Mice with Shn2 deletion(Shn2Δ/Δmice) were obtained by crossing Shn2 floxed mice and telencephalin Cre mice. To confirm the deletion of the exon have the effect similar to Shn2 global knockout, we assessed maturity of the dentate gyrus of Shn2 D/D mice. RT-PCR was conducted to measure the expression of genes that are indices of the maturation of the dentate gyrus using the hippocampus of the mice. Dopamine receptor 1A was increased, desmoplakin and tryptophan 2, 3-dioxygenase were decreased in Shn2Δ/Δmice. These results suggest that Shn2Δ/Δmice have immature dentate gyrus in their adult brain.

Research Products

• [Journal Article] DRPLA transgenic mouse substrains carrying single copy of full-length mutant human DRPLA gene with variable sizes of expanded CAG repeats exhibit CAG repeat length-and age-dependent changes in behavioral abnormalities and gene expression profiles (2012)
  • Author(s): Suzuki K, Zhou J, Sato T, Takao K, Miyakawa T, Oyake M, Yamada M, Takahashi H, Takahashi Y, Goto J, Tsuji S
  • Journal Title: Neurobiology of Disease Volume: Vol.46 Pages: 336-350
  • Peer Reviewed
• [Journal Article] T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice (2012)
  • Author(s): Shoji H, Hagihara H, Takao K, Hattori S, Miyakawa T
  • Journal Title: Journal of Visualized Experiments Volume: Vol.60 Pages: e3300
  • 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, Mark Taketo, Miyakawa T
  • Journal Title: Frontiers in Behavioral Neuroscience Volume: 5 Pages: 85
  • 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: Molecular Brain Volume: 4 Pages: 39
  • 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: Frontiers in Behavioral Neuroscience Volume: 5 Pages: 50
  • 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 Pages: e21050
  • Peer Reviewed
• [Journal Article] Forebrain-specific constitutively active CaMKKαtransgenic mice show deficits in hippocampus-dependent long-term memory (2011)
  • Author(s): Kaitsuka T, Li ST, Nakamura K, Takao K, Miyakawa T, Matsushita M
  • Journal Title: Neurobiology of Learning and Memory Volume: Vol.96 Pages: 238-247
  • Peer Reviewed
• [Journal Article] Synaptic E3 Ligase SCRAPPER in Contextual Fear Conditioning : Extensive Behavioral Phenotyping of Scrapper Heterozygote and Overexpressing Mutant Mice (2011)
  • Author(s): Yao I, Takao K, Miyakawa T, Ito S, Setou M
  • Journal Title: PLoS One Volume: Vol.6 Pages: e17317
  • Peer Reviewed
• [Journal Article] The influence of chronic cerebral hypoperfusion on cognitive function and amyloidβmetabolism in APP overexpressing mice (2011)
  • Author(s): Yamada M, Ihara M, Okamoto Y, Maki T, Washida K, Kitamura A, Hase Y, Ito H, Takao K, Miyakawa T, Kalaria RN, Tomimoto H, Takahashi R
  • Journal Title: PLoS One Volume: Vol.6 Pages: e16567
  • Peer Reviewed
• [Journal Article] Inactivation of fibroblast growth factor binding protein 3 causes anxiety-related behaviors (2011)
  • Author(s): Yamanaka Y, Kitano A, Takao K, Prasansuklab A, Mushiroda T, Yamazaki K, Kumada T, Shibata M, Takaoka Y, Awaya T, Kato T, Abe T, Iwata N, Miyakawa T, Nakamura Y, Nakahata T, Heike T
  • Journal Title: Molecular and Cellular Neuroscience Volume: Vol.46 Pages: 200-212
  • Peer Reviewed
• [Journal Article] Decreased exploratory activity in a mouse model of 15q duplication syndrome ; implications for disturbance of serotonin signaling (2010)
  • Author(s): Tamada K, Tomonaga S, Hatanaka F, Nakai N, Takao K, Miyakawa T, Nakatani J, Takumi T
  • Journal Title: PLoS One Volume: Vol.5 Pages: e15126
  • Peer Reviewed
• [Journal Article] Comprehensive behavioural study of GluR4 knockout mice : implication in cognitive function (2010)
  • Author(s): Sagata N, Iwaki A, Aramaki T, Takao K, Kura S, Tsuzuki T, Kawakami R, Ito I, Kitamura T, Sugiyama H, Miyakawa T, Fukumaki Y
  • Journal Title: Genes, Brain and Behavior Volume: Vol.9 Pages: 899-909
  • Peer Reviewed
• [Journal Article] Expression of tryptophan 2, 3-dioxygenase in mature granule cells of the adult mouse dentate gyrus (2010)
  • Author(s): Ohira K, Hagihara H, Toyama K, Takao K, Kanai M, Funakoshi H, Nakamura T, Miyakawa T
  • Journal Title: Molecular brain Volume: Vol.3, 1 Pages: 26
  • Peer Reviewed
• [Journal Article] 精神疾患の中間表現型としての未成熟歯状回 (2010)
  • Author(s): 高雄啓三、宮川剛
  • Journal Title: 日本神経精神薬理学雑誌 Volume: 30巻 Pages: 115-122
  • Peer Reviewed
• [Journal Article] Stress-evoked tyrosine phosphorylation of signal regulatory protein alpha regulates behavioral immobility in the forced swim test (2010)
  • Author(s): Ohnishi H, Murata T, Kusakari S, Hayashi Y, Takao K, Maruyama T, Ago Y, Koda K, Jin FJ, Okawa K, Oldenborg PA, Okazawa H, Murata Y, Furuya N, Matsuda T, Miyakawa T, Matozaki T
  • Journal Title: The Journal of Neuroscience Volume: Vol.30 Pages: 10472-10483
  • Peer Reviewed
• [Journal Article] Behavioral profiles of three C57BL/6 substrains (2010)
  • Author(s): Matsuo N, Takao K, Nakanishi K, Yamasaki N, Tanda K, Miyakawa T
  • Journal Title: Frontiers in Behavioral Neuroscience Volume: Vol.4 Pages: 29
  • Peer Reviewed
• [Journal Article] SDOP-DB : a comparative standardized-protocol database for mouse phenotypic analyses (2010)
  • Author(s): Tanaka N, Waki K, Kaneda H, Suzuki T, Yamada I, Furuse T, Kobayashi K, Motegi H, Toki H, Inoue M, Minowa O, Noda T, Takao K, Miyakawa T, Takahashi A, Koide T, Wakana S, Masuya H
  • Journal Title: Bioinformatics Volume: Vol.26 Pages: 1133-1134
  • Peer Reviewed
• [Presentation] Mice lacking Schnurri-2 displayed cortical abnormalities related to schizophrenia (2011)
  • Author(s): Takao K, Hagihara H, Ohira K, Toyama K, Takagi T, Ishii S, Miyakawa T
  • Organizer: Neuroscience 2011
  • Place of Presentation: Washington Convention Center, U.S.A
  • Year and Date: 20111112-16
• [Presentation] 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, Tsukiya K, Karatsu Y, Iwamoto Y, Miyakawa T, Suhara T, Trojanowski JQ, Lee VM, Takahashi R
  • Organizer: Neuroscience 2011
  • Place of Presentation: Washington Convention Center, U.S.A
  • Year and Date: 20111112-16
• [Presentation] Synaptic E3 ligase SCRAPPER is crucial for hippocampus-dependent fear memory formation (2011)
  • Author(s): Yao I, Takao K, Miyakawa T, Ito S, Setou M
  • Organizer: Neuroscience 2011
  • Place of Presentation: Washington Convention Center, U.S.A
  • Year and Date: 20111112-16
• [Presentation] Deficiency of Schnurri-2 confers schizophrenia-related phenotypes and inflammatory-like phenomenon in the brain (2011)
  • Author(s): Takao K
  • Organizer: KSBNS-MCCS-Asia Conference
  • Place of Presentation: ソウル大学, Korea
  • Year and Date: 20110919-20
• [Presentation] Mice lacking Schnurri-2 displayed cortical abnormalities related to schizophrenia (2011)
  • Author(s): Takao K, Hagihara H, Kobayashi K, Ohira K, Toyama K, Takagi T, Ishii S, Miyakawa T
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜,横浜市
  • Year and Date: 20110914-17
• [Presentation] Mice lacking Schnurri-2 show schizophrenia-related phenotypes and inflammatory-like responses in the brain (2011)
  • Author(s): Takao K, Kobayashi K, Hagihara H, Ohira K, Toyama K, Shoji H, Nakamura H, Furuya S, Takagi T, Ishii S, Miyakawa T
  • Organizer: The 6th International Conference of Neurons and Brain Disease
  • Place of Presentation: 富山ANAクラウンプラザ,富山市
  • Year and Date: 20110803-05
• [Presentation] MAGI-1 modulates anxiety-like behavior in mice (2010)
  • Author(s): 辻川幸,谷口幸雄,高雄啓三,宮川剛,前川真吾,小林茂夫,二宮治明,眞崎知生,垣塚彰,細川浩
  • Organizer: BMB2010
  • Place of Presentation: 神戸国際会議場,神戸市
  • Year and Date: 20101207-10
• [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): Takao K, Kobayashi K, Hagihara H, Ohira K, Nakamura H, Yamasaki N, Toyama K, Komada M, Takagi T, Ishii S, Miyakawa T
  • Organizer: Neuroscience 2010
  • Place of Presentation: San Diego, U.S.A
  • Year and Date: 20101113-17
• [Presentation] Proteomic analysis of the hippocampus of animal models of psychiatric disorders (2010)
  • Author(s): Hagihara H, Takao K, Toyama K, Nakamura M, Takasaki A, Hashimoto K, Hayashi N, Takagi T, Ishii S, Miyakawa T
  • Organizer: Neuroscience 2010
  • Place of Presentation: San Diego, U.S.A
  • Year and Date: 20101113-17
• [Presentation] Immature dentate gyrus as a candidate endophenotype of psychiatric disorders (2010)
  • Author(s): Hagihara H, Kobayashi K, Ohira K, Toyama K, Takagi T, Isabella AG, Ishii S, Suzuki H, Gerald RC, Takao K, Miyakawa T
  • Organizer: Molecular Cellular Cognition Society
  • Place of Presentation: San Diego, U.S.A
  • Year and Date: 20101111-12
• [Presentation] Behavioral profiles of three C57BL/6 substrains (2010)
  • Author(s): 高雄啓三,松尾直毅,中西和男,山崎信幸,短田浩一,宮川剛
  • Organizer: Neuro2010
  • Place of Presentation: 神戸国際会議場,神戸市
  • Year and Date: 20100902-04
• [Presentation] Expression of Tryptophan 2, 3-Dioxygenase in Mature Granule Cells of the Adult Mouse Dentate Gyrus (2010)
  • Author(s): Ohira K, Hagihara H, Toyama K, Takao K, Kanai M, Funakoshi H, Nakamura T, Miyakawa T
  • Organizer: Neuro2010
  • Place of Presentation: 神戸国際会議場,神戸市
  • Year and Date: 20100902-04
• [Presentation] Proteome analysis of the hippocampus of animal models of psychiatric disorders (2010)
  • Author(s): Hagihara H, Takao K, Toyama K, Nakamura M, Takasaki A, Hashimoto K, Hayashi, N, Miyakawa T
  • Organizer: Neuro2010
  • Place of Presentation: 神戸国際会議場,神戸市
  • Year and Date: 20100902-04
• [Presentation] Behavioral analysis of knockout mice for F-box protein (2010)
  • Author(s): Yao1 I, Takao K, Miyakawa T, Ito S, Setou M
  • Organizer: Neuro2010
  • Place of Presentation: 神戸国際会議場,神戸市
  • Year and Date: 20100902-04
• [Presentation] Increase in ATP release from astrocytes results in increase in the excitability of the hippocampus (2010)
  • Author(s): Tanaka K, Yamazaki Y, Lee H. U, Furuya K, Hida H, Takao K, Miyakawa T, Fujii S, Ikenaka K
  • Organizer: Neuro2010
  • Place of Presentation: 神戸国際会議場,神戸市
  • Year and Date: 20100902-04
• [Presentation] A brain-behavior phenotype database consisting of data derived from comprehensive behavioral analyses of genetically engineered (2010)
  • Author(s): Takao K, Nakanishi K, Miyakawa T
  • Organizer: Neuroinformatics 2010 3rd INCF Congress of Neuroinformatics
  • Place of Presentation: 神戸国際会議場,神戸市
  • Year and Date: 20100830-0901
• [Presentation] Immature dentate gyrus as a candidate endophenotype of psychiatric disorders (2010)
  • Author(s): Takao K, Kobayashi K, Hagihara H, Ohira K, Toyama K, Takagi T, Graef IA, Suzuki H, Crabtree GR, Miyakawa T
  • 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 as a potential endophenotype for psychiatric disorders (2010)
  • Author(s): Takao K, Hagihara H, Ohira K, Matsuo N, Kobayashi K, Toyama K, Takagi T, Ishii S, Suzuki H, Miyakawa T
  • Organizer: 日本分子生物学会,第12回春季シンポジウム
  • Place of Presentation: 松島,宮城県宮城郡
  • Year and Date: 20100607-08
• [Presentation] Behavioral profiles of three C57BL/6 substrains (2010)
  • Author(s): Takao K, Nakanishi K, Yamasaki N, Tanda K, Matsuo N, Miyakawa T
  • Organizer: Society-Genes, Brain & Behavior 12th Annual Meeting
  • Place of Presentation: Dalhousie University, Halifax, Canada
  • Year and Date: 20100512-16
• [Presentation] APC1638Tマウスにみられる空間記憶障害 (2010)
  • Author(s): 尾之内高慶,高雄啓三,宮川剛,千田隆夫
  • Organizer: コ・メディカル形態機能学会第9回学術集会
  • Place of Presentation: 新潟大学,新潟市
  • Year and Date: 2010-09-11
• [Book] 第2章A-10マウスの行動解析と遺伝子,神庭重信,加藤忠史編,「専門医のための精神科臨床リュミエール16、脳科学エンッセンシャル-精神疾患の生物学的理解のために」 (2010)
  • Author(s): 高雄啓三,服部聡子,宮川剛
  • Total Pages: 164-166
  • Publisher: 中山書店