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Analysis of brain functions of PACAP using its specific receptor PAC1 transgenic mice.

Research Project

Project/Area Number 19500368
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionShowa University

Principal Investigator

ARATA Satoru  Showa University, 遺伝子組換え実験室, 准教授 (20159502)

Co-Investigator(Kenkyū-buntansha) ONIMARU Hiroshi  昭和大学, 医学部, 准教授 (30177258)
TAKETOMI Yoshitaka  昭和大学, 遺伝子組換え実験室, 助教 (40365804)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords病態モデル / PACAP / トランスジェニックマウス / 行動解析 / 発生工学 / 高次神経機能 / 行動生理 / PAC1 / 学習・記憶 / サーカディアン
Research Abstract

To define the physiological roles of pituitary adenylate cyclase-activating polypeptide (PACAP), we developed the PACAP-preferring receptor (PAC1) transgenic (Tg) mice using the Cre/loxP recombination system. The three type of PAC1 Tg mice which were expressed the Pac1 transgene in the whole body (wPAC1 Tg mice), in the hippocampus (hPAC1 Tg mice), and in the hippocampus after tamoxifen treatment (ihPAC1 Tg mice), were obtained.
We studied here the physiological roles of PACAP in brain using these PAC1 Tg mice. The spontaneous motor activity in home cage, the PAC1 expression, especially in hippocampus, increased behavioral activity at early dark period (ZT 12-17) which is most active time zone of the wild type mice. Furthermore, on the aged-mice which generally depressed motor activity, hPAC1 Tg mice showed more active with a clockwork circadian rhythm. These results suggest that the expression of PAC1 transgene, especially in the hippocampus nerve cells, make to enhance the behavioral activity with regular circadian rhythm. On the other hand, we studied the effect of PACAP in developmental respiratory adaptation by whole-body plethysmography and ex vivo analysis using brainstem-spinal cord preparation. Although this study is primitive, up to now, it was suggested that PACAP signaling concerned the development of central respiratory rhythmgensis.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (38 results)

All 2010 2009 2008 2007

All Journal Article (17 results) (of which Peer Reviewed: 13 results) Presentation (19 results) Book (2 results)

  • [Journal Article] Central respiratory failure in a mouse model depends on the genetic background of the host.2010

    • Author(s)
      Arata S, Amano K, Yamakawa K, Arata A.
    • Journal Title

      Adv Exp Med Biol. 669

      Pages: 21-24

    • Related Report
      2009 Final Research Report
  • [Journal Article] Loss of Pre-Inspiratory Neuron Synchroneity in Mice with DSCAM Deficiency2010

    • Author(s)
      Amano K, Fujii M, Arata S, Ogawa M, Yamakawa K, Arata A
    • Journal Title

      Adv Exp Med Biol. 669

      Pages: 15-19

    • Related Report
      2009 Final Research Report
  • [Journal Article] Central respiratory failure in a mouse model depends on the genetic background of the host2010

    • Author(s)
      ARATA Satoru
    • Journal Title

      Adv Exp Med Biol 669

      Pages: 21-24

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Loss of Pre-Inspiratory Neuron Synchroneity in Mice with DSCAM Deficiency2010

    • Author(s)
      AMANO Kenji
    • Journal Title

      Adv Exp Med Biol. 669

      Pages: 15-19

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Transient increase in plasma oxidized LDL during the progression of atherosclerosis in apolipoprotein E knockout mice.2009

    • Author(s)
      Kato R, Mori C, Kitazato K, Arata S, Obama T, Mori M, Takahashi K, Aiuchi T, Takano T, Itabe H.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 29(1)

      Pages: 33-9

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Arata SDSCAM deficiency causes loss of pre-inspiratory neuron synchroneity and perinatal death.2009

    • Author(s)
      Amano K, Fujii M, Tojima T, Ogawa M, Morita N, Shimohata A, Furuichi T, Itohara S, Kamiguchi H, Korenberg JR, Arata A, Yamakawa K.
    • Journal Title

      J Neurosci. 29(9)

      Pages: 2984-96

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Arata SDepletion of selenoprotein GPx4 in spermatocytes causes male infertility in mice.2009

    • Author(s)
      Imai H, Hakkaku N, Iwamoto R, Suzuki J, Suzuki T, Tajima Y, Konishi K, Minami S, Ichinose S, Ishiizaka K, Shioda S, Nishimura M, Naito S, Nakagawa Y.
    • Journal Title

      J Biol Chem. 284(47)

      Pages: 32522-32

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Depletion of selenoprotein GPx4 in spermatocytes causes male infertility in mice2009

    • Author(s)
      IMAI Hirotaka
    • Journal Title

      J Biol Chem 284

      Pages: 32522-32532

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DSCAM deficiency causes loss of pre-inspiratory neuron synchroneity and perinatal death2009

    • Author(s)
      Amano Kenji
    • Journal Title

      J Neurosci. 4

      Pages: 2984-2996

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transient increase in plasma oxidized LDL during the progression of atherosclerosis in apolipoprotein E knockout mice2009

    • Author(s)
      Kato Rina
    • Journal Title

      Arterioscler Thromb Vase Biol. 29

      Pages: 33-39

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Visualization of ghrelin-producing neurons in the hypothalamic arcuate nucleus using ghrelin-EGFP transgenic mice.2008

    • Author(s)
      Kageyama, H, Kitamura, Y, Hosono, T, Kintaka, Y, Seki, M, Takenoya, F, Hori, Y, Nonaka, N, Arata, S, Shioda, S
    • Journal Title

      Regul Pept. 145

      Pages: 116-21

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Visualization of ghrelin-producing neurons in the hypothalamic arcuate nucleus using ghrelin-EGFP transgenic mice2008

    • Author(s)
      Kageyama Haruaki
    • Journal Title

      Regul Pept. 145

      Pages: 116-121

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Arata S Generation of muscle aquaporin 4 overexpressing transgenic mouse: Its characterization at RNA and protein levels including freeze-fracture study.2007

    • Author(s)
      Wakayama Y, Takahashi J, Shibuya S, Inoue M, Kojima H, Oniki H, Hara H, Jimi T, Shioda S, Sunada Y, Ohi H, Shimizu T.
    • Journal Title

      Micron. Micron. 38(3)

      Pages: 257-267

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impaired mast cell maturation and degranulation and attenuated allergic responses in Ndrg1-deficient mice.2007

    • Author(s)
      Taketomi YTanaka S, Sunaga K,, Nakamura M, Arata S, Okuda T, Moon TC, Chang HW, Sugimoto Y, Kokame K, Miyata T, Murakami M, Kudo I.
    • Journal Title

      J Immunol. 178(11)

      Pages: 7042-7042

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impaired mast cell maturation and degranulation and attenuated allergic responses inNdrg l-deficient mice2007

    • Author(s)
      Taketomi Y, et. al.
    • Journal Title

      J Immunol. 178・11

      Pages: 7042-7053

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of muscle aquaporin 4 0verexpressing transgenic mouse:Its characterization at RNA and protein levels including freeze-fracture study2007

    • Author(s)
      Wakayama Y, et. al.
    • Journal Title

      Micron 38・3

      Pages: 257-267

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defective interaction between dual oscillators for respiratory rhythm generation in Na^+,K^+-ATPase {alpha}2 subunit-deficient mice2007

    • Author(s)
      Onimal H, et. al.
    • Journal Title

      J. Physiol 584

      Pages: 271-284

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 新生期マウスの呼吸馴化における系統の差異2009

    • Author(s)
      荒田悟、荒田晶子、武富芳隆、細野知彦、鬼丸洋、塩田清二
    • Organizer
      第56回日本実験動物学会総会
    • Place of Presentation
      大宮
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] マウス脳虚血モデルを用いた内因性PACAPの神経細胞死抑制作用の解析2009

    • Author(s)
      中町智哉、大滝博和、養父佐知子、野中直子、荒田悟、William A. Banks、塩田清二
    • Organizer
      第56回日本実験動物学会総会
    • Place of Presentation
      大宮
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] DSCAM deficiency causes loss of pre-inspiratory neuron synchroneity and perinatal death2009

    • Author(s)
      Amano K, Fujii M, Arata S, Yamakawa K, Arata A
    • Organizer
      11th Oxford
    • Place of Presentation
      Nara
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] Occurrence of central respiratory failure in mouse model depend on host genetic background2009

    • Author(s)
      Arata S, Amano K, Yamakawa K, Arata A
    • Organizer
      11th Oxford
    • Place of Presentation
      Nara
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] PACAP特異的受容体(PAC1)トランスジェニックマウスにおける自発行動の亢進2008

    • Author(s)
      荒田 悟
    • Organizer
      第31回 日本分子生物学会2008
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] III型ホスホリパーゼA2は即時型アレルギーに関与する2008

    • Author(s)
      武富 芳隆
    • Organizer
      BMB2008(日本生化学会年会)
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] Increased behavioral activity with regular circadian rhythm in PACAP specific receptor (PAC1) transgenic mice.2008

    • Author(s)
      S. Arata, T. Hosono, Y. Taketomi, H. Kageyama, T. Nakamachi, S. Shioda.
    • Organizer
      5th Showa International Symposium
    • Place of Presentation
      Tokyo
    • Year and Date
      2008-09-02
    • Related Report
      2009 Final Research Report
  • [Presentation] Increased behavioral activity with regular circadian rhythm in PACAP specific receptor (PAC1)transgenic mice2008

    • Author(s)
      ARATA Satoru
    • Organizer
      5th Showa International Symposium
    • Place of Presentation
      Tokyo
    • Year and Date
      2008-09-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] Group III PLA2 is a critical regulator of mast cell differentiation and activation2008

    • Author(s)
      TAKETOMI Yoshitaka
    • Organizer
      2008 FASEB Summer Research Conference
    • Place of Presentation
      Connecticut, USA
    • Year and Date
      2008-07-22
    • Related Report
      2008 Annual Research Report
  • [Presentation] Difference of EGFR-binding proteins between wild type and mutant EGFR2008

    • Author(s)
      KADOFUKU Tsuyoki
    • Organizer
      AACR 2008
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2008-04-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] III型分泌性ホスホリパーゼA2は即時性アレルギーに関与する2008

    • Author(s)
      武富芳隆、川名桃子、佐藤弘泰、田中智之、上野紀子、山本圭、荒田悟、原俊太郎、工藤一郎、村上誠
    • Organizer
      第9回Pharmaco-Hematologyシンポジウム
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report 2008 Annual Research Report
  • [Presentation] PACAP特異的受容体(PAC1)トランスジェニックマウスにおける自発行動の亢進2008

    • Author(s)
      荒田悟、細野知彦、武富芳隆、影山晴秋、中町智哉、塩田清二
    • Organizer
      第31回日本分子生物学会
    • Place of Presentation
      神戸
    • Related Report
      2009 Final Research Report
  • [Presentation] III型ホスホリパーゼA2は即時型アレルギーに関与する2008

    • Author(s)
      武富芳隆、川名桃子、佐藤弘泰、田中智之、山本圭、荒田悟、原俊太郎、工藤一郎、村上誠
    • Organizer
      BMB2008
    • Place of Presentation
      神戸
    • Related Report
      2009 Final Research Report
  • [Presentation] PACAP受容体(PAC1)トランスジェニックマウスにおける自発行動の亢進について2007

    • Author(s)
      荒田悟、影山晴秋、中町智哉、武富芳隆、細野知彦、塩田清二
    • Organizer
      第54回日本実験動物学会総会
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report
  • [Presentation] 膜結合型Ca2+非依存性ホスホリパーゼA2(iPLA2γ)の解析2007

    • Author(s)
      依田恵美子、小林裕司、藤本知佳子、桑田浩、武富芳隆、荒田悟、中谷良人、原俊太郎、工藤一郎
    • Organizer
      第49回日本脂質生化学会
    • Place of Presentation
      北海道
    • Related Report
      2009 Final Research Report
  • [Presentation] マスト細胞の成熟に伴って発現誘導されるNDRG1の解析2007

    • Author(s)
      武富芳隆、須永剛平、田中智之、中村雅典、荒田悟、奥田智彦、杉本幸彦、小亀浩市、宮田敏行、村上誠、工藤一郎
    • Organizer
      第8回Pharmaco-Hematologyシンポジウム
    • Place of Presentation
      金沢
    • Related Report
      2009 Final Research Report
  • [Presentation] Visualization of ghrelin-producing neurons in the hypothalamic arcuate nucleus using the ghrelin-enhanced green fluorescent protein transgenic mice.2007

    • Author(s)
      Kageyama H, Hosono T, Arata S, Takenoya F, Shioda S.
    • Organizer
      Neuroscience 2007
    • Place of Presentation
      San Diego
    • Related Report
      2009 Final Research Report
  • [Presentation] Loss of Pre-inspiratory neuron synchroneity in mice with Dscam1 deficiency.2007

    • Author(s)
      Amano K, Fujii M, Tojima T, Ogawa M, Morita N, Arata S, Shimohata A, Furuichi T, Itohara S, Kamiguchi H, J R Korenberg, Arata A, Yamakawa K
    • Organizer
      Neuroscience 2007
    • Place of Presentation
      San Diego
    • Related Report
      2009 Final Research Report
  • [Presentation] Visualization of ghrelin-producing neurons in the hypothalamic arcuate nucleus usingthe ghrelin-enhanced green fluorescent protein transgenic mice2007

    • Author(s)
      Kageyama H, et. al.
    • Organizer
      Neuroscience 2007
    • Place of Presentation
      San Diego,USA
    • Related Report
      2007 Annual Research Report
  • [Book] Transmitters and Modulators in Heaith and Disease(S. Shioda, I. Homma, N. Kato editors., Increased behavioral activity with regular circadian rhythm in PACAP specific receptor (PAC1) transgenic mice)2009

    • Author(s)
      Arata S, Hosono T, Taketomi Y, Kageyama H, Nakamachi T, Shioda S.
    • Publisher
      Springer-Verlag
    • Related Report
      2009 Final Research Report
  • [Book] Transmitters and Modulators in Health and Disease2009

    • Author(s)
      Arata Satoru, et al. (S. Shioda, I. Homma, N. kato (Eds. ))
    • Total Pages
      212
    • Publisher
      Springer
    • Related Report
      2008 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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