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Molecular analysis of mast cell activation in mouse models for autoinflammatory syndromes and its use for anti-inflammatory drug development

Research Project

Project/Area Number 25290036
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Laboratory animal science
Research InstitutionTokai University

Principal Investigator

ABE Koichiro  東海大学, 医学部, 准教授 (90294123)

Co-Investigator(Kenkyū-buntansha) RA Chisei  日本大学, 医学部, 客員教授 (60230851)
TAJIMA Atsushi  金沢大学, 医薬保健研究域, 教授 (10396864)
Co-Investigator(Renkei-kenkyūsha) NUNOMURA Satoshi  佐賀大学, 医学部, 助教 (70424728)
KIMURA Minoru  東海大学, 医学部, 教授 (10146706)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Keywords病態モデル / 関節炎 / 自然炎症 / 変異マウス / 疾患モデル / ミュータジェネシス / 遺伝学 / 実験動物学 / マウス遺伝学 / 疾患モデル動物 / ENUミュータジェネシス
Outline of Final Research Achievements

Autoinflammation syndromes are caused by an exaggerated innate immune system response without autoatibodies and selfreactive T cells, and the patients show spontaneous inflammation affecting multiple organs. The Ali14 and Ali18 are gain-of-function mutations in cell signaling effector enzyme genes, and trigger inflammation through the innate immune cells by unknown mechanisms. Because the double mutant with Ali18 and W/Wv , which lacks mast cell population, did not show autoinflammation, we analyzed cultured mast cells from mutant bone marrow.Ali14 and Ali18 mast cells showed lower calcium concentration for antigen stimulation. Further, micro-array analysis identified 1124 and 750 up-regulated genes specifically in Ali18 and Ali14 mast cells, respectively. Further, 127 genes were up-regulated in both mutant mast cells. Cell signaling pathways involving these up-regulated genes might provide insight into extensive repression against autoinflammation.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (36 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (15 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (7 results)

  • [Int'l Joint Research] Hemholtz Zentrum Muenchen(ドイツ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Conditional knockout of Foxc2 gene in kidney; efficient generation of conditional alleles of single-exon gene by double-selection system.2016

    • Author(s)
      Motojima M, Ogiwara S, Matsusaka T, Kim SY, Sagawa N, Abe K, Ohtsuka M.
    • Journal Title

      Mammalian Genome

      Volume: 27 Pages: 62-69

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CRISPR/Cas9-mediated gene knockout in the mouse brain using in utero electroporation2016

    • Author(s)
      Shinmyo Y., Tanaka S., Tsunoda S., Hosomichi K., Tajima A. and Kawasaki H.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 20611-20611

    • DOI

      10.1038/srep20611

    • NAID

      120005764199

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Novel ENU-induced mutation in Tbx6 causes dominant spondylocostal dysostosis-like vertebral malformations in the rat.2015

    • Author(s)
      Abe K, Takamatsu N, Ishikawa K, Tsurumi T, Tanimoto S, Sakurai Y, Lisse T, Serikawa T, Mashimo T.
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 6 Pages: e0130231-e0130231

    • DOI

      10.1371/journal.pone.0130231

    • NAID

      120005947155

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Disappearance of centroacinar cells in the Notch ligand-deficient pancreas.2015

    • Author(s)
      Nakano Y, Negishi N, Gocho S, Mine T, Sakurai Y, Yazawa M, Abe K, Yagita H, Habu S, Kageyama R, Kawaguchi Y, Hozumi K.
    • Journal Title

      Genes to Cells

      Volume: 33 Issue: 6 Pages: 500-511

    • DOI

      10.1111/gtc.12243

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of nuclear hormone receptors in cutaneous wound repair.2015

    • Author(s)
      Rieger S, Hengguang Zhao, Paige Martin, Abe K, Lisse TS.
    • Journal Title

      Cell Biochemistry and Function

      Volume: 33 Issue: 1 Pages: 1-13

    • DOI

      10.1002/cbf.3086

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Activation of LXRs using the synthetic agonist GW3965 represses the production of pro-inflammatory cytokines by murine mast cells.2015

    • Author(s)
      Nunomura S, Okayama Y, Matsumoto K, Hashimoto N, Endo-Umeda K, Terui T, Makishima M, Ra C.
    • Journal Title

      Allergology International

      Volume: 64S

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Highly expressed cytoplasmic FcεRIβ in human mast cells functions as a negative regulator of the FcRγ-mediated cell activation signal.2014

    • Author(s)
      Okayama Y, Matsuda A, Kashiwakura JI, Sasaki-Sakamoto T, Nunomura S, Shimokawa T, Yamaguchi K, Takahashi S, Ra C.
    • Journal Title

      Clin Exp Allergy

      Volume: 44 Pages: 238-249

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] C/EBPα controls functions of mast cells.2014

    • Author(s)
      4. Kasakura K, Takahashi K, Itoh T, Hosono A, Nunomura S, Ra C, Momose Y, Itoh K, Nishiyama C, Kaminogawa S.
    • Journal Title

      FEBS Letters

      Volume: 588 Pages: 4645-4653

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiling reveals distinct molecular signatures associated with the rupture of intracranial aneurysm.2014

    • Author(s)
      Nakaoka H, Tajima A, Yoneyama T, Hosomichi K, Kasuya H, Mizutani T, Inoue I.
    • Journal Title

      Stroke

      Volume: 45 Pages: 2239-2245

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Estrogen promotes Leydig cell engulfment by macrophages in male infertility.2014

    • Author(s)
      Yu W, Zheng H, Lin W, Tajima A, Zhang Y, Zhang X, Zhang H, Wu J, Han D, Rahman NA, Korach KS, Gao GF, Inoue I, Li X.
    • Journal Title

      J Clin Invest

      Volume: 124 Pages: 2709-2721

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fc receptor beta chain deficiency exacerbates murine arthritis in the anti-type II collagen antibody-induced experimental model2013

    • Author(s)
      Ohtsubo-Yoshioka M, Nunomura S, Kataoka TR, Okayama Y, Ra CS
    • Journal Title

      Modern Rheumatolog

      Volume: 23 Pages: 804-810

    • NAID

      10031189177

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of the C/EBP alpha C-terminal tail residues involved in the protein interaction with GABP and their potency in myeloid differentiation of K562 cells2013

    • Author(s)
      Shimokawa T, Nunomura S, Fujisawa D, Ra CS
    • Journal Title

      Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms

      Volume: 1829 Pages: 1207-1217

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TRIM39, but not TRIM39B, regulates type I interferon response.2013

    • Author(s)
      Riho Kurata, Atsushi Tajima, Tomo Yonezawa and Hidetoshi Inoko
    • Journal Title

      Biochemcal and Biophysical Research Communications

      Volume: 436 Issue: 1 Pages: 90-95

    • DOI

      10.1016/j.bbrc.2013.05.064

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 発現量に基づいた新規がん予後予測遺伝子群の探索2015

    • Author(s)
      丹下正一朗、田嶋敦
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Abnormal innate immune responses of ENU-induced Ali18 and Ali14 mutant mice lead to autoinflammatory syndrome-like phenotypes.2015

    • Author(s)
      Abe K, Nunomura S, Ra C, Tajima A, Fuchs H, Hrabě de Angelis M.
    • Organizer
      29th International Mammalian Genome Conference
    • Place of Presentation
      横浜市開港記念会館(神奈川県横浜市)
    • Year and Date
      2015-11-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ENUミュータジェネシスにおいて単離されたマウスモデルによる自己炎症性弛緩発症機構の解析2015

    • Author(s)
      阿部幸一郎
    • Organizer
      日本遺伝学会第87回大会
    • Place of Presentation
      東北大学川内北キャンパス(宮城県仙台市)
    • Year and Date
      2015-09-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 自己炎症性症候群モデルマウスにおける自然免疫系のシグナル伝達異常による炎症発生機構の解析2015

    • Author(s)
      阿部幸一郎、布村聡、羅智靖、田嶋敦
    • Organizer
      第62回日本実験動物学会総会
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Year and Date
      2015-05-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞膜発現FcεRIα鎖蛋白との反応性を利用した抗FcεRIα鎖抗体検出法の慢性蕁麻疹患者における有用性2015

    • Author(s)
      伊崎 聡志,布村 聡,藤澤 大輔,畠田 優子,葉山 惟大,藤田 英樹,羅 智靖,岡山 吉道,照井 正
    • Organizer
      第64回日本アレルギー学会秋季学術大会
    • Place of Presentation
      国立成育医療研究センター研究所(東京都世田谷区)
    • Year and Date
      2015-05-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] FcRγ promotes contact hypersensitivity to oxazolone without affecting the contact sensitization process2014

    • Author(s)
      Nunomura S, Okayama Y, Terui T, Ra C
    • Organizer
      第43回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] 精神運動発育遅滞を伴う家族性小脳失調症で見つかったVWA3B遺伝子変異2014

    • Author(s)
      瓦井俊孝、田嶋敦、黒田由紀子、佐治直樹、寺澤英夫、清水洋孝、喜多也寸志、アントニオオラッキオ、宮本亮介、和泉唯信、三ツ井貴夫、井本逸勢、梶龍兒
    • Organizer
      日本人類遺伝学会第59回大会・日本遺伝子診療学会第21回大会 合同大会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-19 – 2014-11-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 好中球分化におけるC/EBPαのC 末端領域の解析2014

    • Author(s)
      下川敏文,布村聡,藤澤大輔,羅智靖
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-10-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] 自己炎症性症候群モデルマウスにおける自然免疫系異常による炎症発生機構の解析2014

    • Author(s)
      阿部幸一郎、布村聡、羅智靖、田嶋敦
    • Organizer
      日本実験動物科学技術2014
    • Place of Presentation
      札幌
    • Year and Date
      2014-05-15 – 2014-05-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] バルプロ酸投与による体節形成関連遺伝子の発現変化に起因した脊柱形態異常の解析2014

    • Author(s)
      谷口真沙美、持田讓治、阿部幸一郎
    • Organizer
      日本実験動物科学技術2014
    • Place of Presentation
      札幌
    • Year and Date
      2014-05-15 – 2014-05-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] TRIM39R, but not TRIM39B regulates type I interferon2013

    • Author(s)
      倉田里穂、田嶋敦、米沢朋、猪子英俊
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] バルプロ酸投与をモデルとしたエピジェネティックな遺伝子発現制御による脊椎形成異常の解析2013

    • Author(s)
      谷口真沙美、阿部幸一郎、檜山明彦、酒井大輔、持田讓治
    • Organizer
      第60回日本実験動物学会総会
    • Place of Presentation
      つくば
    • Related Report
      2013 Annual Research Report
  • [Presentation] ラットにおいて優性遺伝する脊椎形成異常を引き起こすOuneの原因遺伝子同定とその機能解析2013

    • Author(s)
      阿部幸一郎、鶴見東志子、高松信彦、石川久美子、今井賢治、芹川忠夫、真下知士
    • Organizer
      第60回日本実験動物学会総会
    • Place of Presentation
      つくば
    • Related Report
      2013 Annual Research Report
  • [Presentation] Oune, a missense mutation in Tbx6, causes congenital vertebral malformations in the rat2013

    • Author(s)
      Koichiro Abe
    • Organizer
      27th International Mammalian Genome Conference
    • Place of Presentation
      Salamanca, Spain
    • Related Report
      2013 Annual Research Report
  • [Presentation] バルプロ酸投与をモデルとした脊柱形態異常をもたらす環境要因と遺伝子発現制御相互作用の解析2013

    • Author(s)
      谷口真沙美、佐川暢保、川上祥一、酒井大輔、持田讓治、阿部幸一郎
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Remarks] Koichiro Abe's Laboratory

    • URL

      http://abe.med.u-tokai.ac.jp/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] TWAVE, VOL.2-2 骨の疾患、その解明に挑む。

    • URL

      http://www.u-tokai.ac.jp/effort/activity/twave/volume02_2/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 東海大学医学部阿部研究室

    • URL

      http://abe.med.u-tokai.ac.jp/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] TWAVE vol.2-2

    • URL

      http://www.u-tokai.ac.jp/effort/activity/twave/volume02_2/

    • Related Report
      2014 Annual Research Report
  • [Remarks] TWAVE vol.2-2 PDF (English)

    • URL

      http://www.u-tokai.ac.jp/english/common/pdf/TWB_vol.12_2.pdf

    • Related Report
      2014 Annual Research Report
  • [Remarks] 東海大学医学部 阿部幸一郎 研究室

    • URL

      http://abe.med.u-tokai.ac.jp/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] Tokai Univ. TWAVE

    • URL

      http://www.u-tokai.ac.jp/twave/volume02_2/index.html

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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