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Generation of the HCV-infectable mouse-an animal model for inflammation cancer

Research Project

Project/Area Number 24659603
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

MIURA Naoyuki  浜松医科大学, 医学部, 教授 (40165965)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsC型肝炎ウイルス / 複製因子 / 肝細胞癌 / 慢性炎症 / 複製 / 侵入 / ウイルス粒子形成 / ウイルス粒子 / ゲノムRNA / 感染
Research Abstract

Experimental plan expected that short promoter has no transcriptional activity to synthesize HCV genome RNA. Unexpectedly, the transgenic mouse showed that they produce HCV genome RNA in hepatocytes and also viral particles into serum. Using the mouse serum from the transgenic mouse, the virus infected Huh7.5.1 cells and produced Core protein in the cytoplasm. This means that the virus was infectious.
Next we investigated whether the HCV genome RNA can replicate in the mouse hepatocytes. When the replication inhibitor was injected into the abdomen of the mouse, the RNA copy number was decreased by 30% in the hepatocytes and serum. This result showed that mouse replication factor(s) were competent for viral RNA replication as human factor(s) do.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (33 results)

All 2014 2013 2012 Other

All Journal Article (23 results) (of which Peer Reviewed: 11 results) Presentation (9 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Control of retinoid levels by CYP26B1 is important for lymphatic vascular development in the mouse embryo2014

    • Author(s)
      Bowles J, Secker G, Nguyen C, Kazenwadel J, Truong V, Frampton E, Curtis C, Akoczylas R, Davidson T-L, Miura N, Hong Y-K, Koopman P, Harvey NL, Francois M
    • Journal Title

      Dev Biol

      Volume: 386 Pages: 25-33

    • Related Report
      2013 Final Research Report
  • [Journal Article] TGFa, c-MYC, mutated CTNNB1 and their combinations act distinctly on the Hep3B tumors in nude mice2014

    • Author(s)
      Noritake H, Amin MB, Nakamura K, Islam MJ, Wu Y-X, Hashimoto S, Uddin MKM, Suda T, Kobayashi Y, Sugimura H, Miura N
    • Journal Title

      Med J Osaka Univ

      Volume: 56 Pages: 11-21

    • Related Report
      2013 Final Research Report
  • [Journal Article] Control of retinoid levels by CYP26B1 is important for lymphatic vascular development in the mouse embryo.2014

    • Author(s)
      Bowles J at al.
    • Journal Title

      Dev Biol

      Volume: 386 Issue: 1 Pages: 25-33

    • DOI

      10.1016/j.ydbio.2013.12.008

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FOXC2 expression links epitherial-mesenchymal transition and stem cell properties in breast cancer2013

    • Author(s)
      Hollier BG, Tinnirello AA, Werden SJ, Evans KW, Taube JH, Sarker TR, Sphyris N, Shariati M, Kumar SV, Battula VL, Herschkowitz JI, Guerra R, Chang JT, Miura N, Rosen JM, Mani SA
    • Journal Title

      Cancer Res

      Volume: 73 Pages: 1981-1992

    • Related Report
      2013 Final Research Report
  • [Journal Article] Generation and characterization of Tbx1-AmCyan1 transgenic reporter mouse line that selectively labels developing thymus primordium2013

    • Author(s)
      Kimura W, Sharkar MTK, Sultana N, Islam MJ, Uezato T, Miura N
    • Journal Title

      Transgenic Res

      Volume: 22 Pages: 659-666

    • Related Report
      2013 Final Research Report
  • [Journal Article] Foxc2 induces Wnt4 and Bmp4 expression during muscle regeneration and osteogenesis2013

    • Author(s)
      Gozo M, Aspuria P-J, Dong-Joo Cheon, Walts AE, Berel D, Miura N, Karlan BY, Orsulic S
    • Journal Title

      Cell Death Differ

      Volume: 20 Pages: 1031-1042

    • Related Report
      2013 Final Research Report
  • [Journal Article] Phosphorylation regulates FOXC2-mediated transcription in lymphatic endothelial cells2013

    • Author(s)
      Ivanov IK, Agalarov y, Valmu L, Samuilova O, Houhou N, Hajjami MH, Norrmen C, Jaquet M, Miura N, Zangger N, Yla-Herttuala S, Delorenzi M, Petrova TV
    • Journal Title

      Mol Cell Biol

      Volume: 33 Pages: 3749-3761

    • Related Report
      2013 Final Research Report
  • [Journal Article] Baicalin and scutellarin are proteasome inhibitors that specifically target chymotrypsin-like catalytic activity2013

    • Author(s)
      Wu Y-X, Sato E, Kimura W, Miura N
    • Journal Title

      Phytother Res

      Volume: 27 Pages: 1362-1367

    • Related Report
      2013 Final Research Report
  • [Journal Article] Generation and characterization of Tbx1-AmCyan1 transgenic reporter mouse line that selectively labels developing thymus primordium.2013

    • Author(s)
      Kimura W et al.
    • Journal Title

      Transgenic Res

      Volume: 22 Issue: 3 Pages: 659-666

    • DOI

      10.1007/s11248-012-9664-5

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FOXC2 expression links epitherial-mesenchymal transition and stem cell properties in breast cancer.2013

    • Author(s)
      Hollier BG et al.
    • Journal Title

      Cancer Res

      Volume: 73 Issue: 6 Pages: 1981-1992

    • DOI

      10.1158/0008-5472.can-12-2962

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Foxc2 induces Wnt4 and Bmp4 expression during muscle regeneration and osteogenesis.2013

    • Author(s)
      Gozo M et al.
    • Journal Title

      Cell Death Deffer

      Volume: 20 Issue: 8 Pages: 1031-1042

    • DOI

      10.1038/cdd.2013.34

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Baicalin and scutellarin are proteasome inhibitors that specifically target chymotrypsin-like catalytic activity.2013

    • Author(s)
      Yi-Xin Wu, Eiji Sato, Wataru Kimura, Naoyuki Miura
    • Journal Title

      Phytotherapy Res

      Volume: in press Issue: 9 Pages: 1362-1367

    • DOI

      10.1002/ptr.4878

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation regulates FOXC2-mediated transcription in lymphatic endothelial cells.2013

    • Author(s)
      Ivanov IK et al.
    • Journal Title

      Mol Cell Biol

      Volume: 33 Issue: 19 Pages: 3749-3761

    • DOI

      10.1128/mcb.01387-12

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation and characterization of Tbx1-AmCyan1 transgenic reporter mouse line that selectively labels developing thymus primordium.2013

    • Author(s)
      Kimura W, Sharkar MT, Sultana N, Islam MJ, Uezato T, Miura N.
    • Journal Title

      Transgenic Res

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Liver tumor formation by a mutant retinoblastoma protein in the transgenic mice is caused by an up-regulation of c-Myc target genes2012

    • Author(s)
      Wang B, Hikosaka K, Sultana N, Sharkar MTK, Noritake H, Kimura W, Wu Y-X, Kobayashi Y, Uezato T, Miura N
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 417 Pages: 601-606

    • Related Report
      2013 Final Research Report
  • [Journal Article] Screening of natural medicines that efficiently activate neurite outgrowth in PC12 cells in C2C12-cultured medium2012

    • Author(s)
      Uezato T, Sato E, Miura N
    • Journal Title

      Biomed Res

      Volume: 33 Pages: 25-33

    • NAID

      130004470798

    • Related Report
      2013 Final Research Report
  • [Journal Article] Mechanotransduction, PROX1 and FOXC2 cooperate to control connexin 37 and calcineurin during lymphatic valve formation2012

    • Author(s)
      Sabine A, Agalarov Y, Hajjami NME, Jaquet M, Hagerling R, Pollmann C, Bebber D, Pfenniger A, Miura N, Dormond O, Calmes JM, Adams RH, Makinen T, Kiefer F, Kwak BR, Petrova TV
    • Journal Title

      Dev Cell

      Volume: 22 Pages: 430-445

    • Related Report
      2013 Final Research Report
  • [Journal Article] Semaphorin 3A, Neuropilin-1, and PlexinA1 are required for lymphatic valve formation2012

    • Author(s)
      Bouvree K, Brunet I, del Toro R, Gordon E, Prahst C, Cristofaro B, Mathivet T, Xu Y, Soueid J, Fortuna V, Miura N, Aigrot M-S, Maden CH, Ruhrberg C, Thomas JL, Eichmann A
    • Journal Title

      Circ Res

      Volume: 111 Pages: 437-445

    • Related Report
      2013 Final Research Report
  • [Journal Article] The regulation of endogenous retinoic acid level through CYP26B1 is reqired for elevation of palatal shelves2012

    • Author(s)
      Okano J, Kimura W, Papaionnou VE, Miura N, Yamada G, Shiota K, Sakai Y
    • Journal Title

      Dev Dyn

      Volume: 241 Pages: 1744-1756

    • Related Report
      2013 Final Research Report
  • [Journal Article] Liver tumor formation by a mutant retinoblastoma protein in the transgenic mice is caused by an up-regulation of c-Myc target genes2012

    • Author(s)
      Wang B, et al
    • Journal Title

      Biochemica Biophysica Res Commun

      Volume: 417 Issue: 1 Pages: 601-606

    • DOI

      10.1016/j.bbrc.2011.12.014

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation.2012

    • Author(s)
      Sabine A, Agalarov Y, Maby-El Hajjami H, Jaquet M, Hägerling R, Pollmann C, Bebber D, Pfenniger A, Miura N, Dormond O, Calmes JM, Adams RH, Makinen T, Kiefer F, Kwak BR, Petrova TV.
    • Journal Title

      Dev Cell

      Volume: 22 Issue: 2 Pages: 430-445

    • DOI

      10.1016/j.devcel.2011.12.020

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Screening of natural medicines that efficiently activate neurite outgrowth in PC12 cells in C2C12-cultured medium.2012

    • Author(s)
      Uezato T, Sato E, Miura N.
    • Journal Title

      Biomed Res

      Volume: 33 Pages: 25-33

    • NAID

      130004470798

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The regulation of endogenous retinoic acid level through CYP26B1 is required for elevation of palatal shelves.2012

    • Author(s)
      Okano J, Kimura W, Papaionnou VE, Miura N, Yamada G, Shiota K, Sakai Y.
    • Journal Title

      Dev Dyn

      Volume: 241 Issue: 11 Pages: 1744-1756

    • DOI

      10.1002/dvdy.23862

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] TGFα, c-MYC, mutated CTNNB1 and their combinations act distinctly on the Hep3B tumors in nude mice2014

    • Author(s)
      Noritake H, Amin M, Kobayashi Y, Miura N
    • Organizer
      Keystone Sympozium on"Developmental pathways and cancer : Wnt, Notch and Hedgehog"
    • Year and Date
      2014-02-04
    • Related Report
      2013 Final Research Report
  • [Presentation] コンディショナルFoxc2ノックアウトマウスを用いた大血管形成の分子機構の解明2013

    • Author(s)
      三浦直行、木村航、ウディンモハマド、中村佳寿美
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      横浜(シンポジウム)
    • Year and Date
      2013-09-11
    • Related Report
      2013 Final Research Report
  • [Presentation] The loss of Foxc2 in the outflow tract links the interrupted arch in the conditional Foxc2 knockout mouse2013

    • Author(s)
      Uddin MKM, Kimura W, Amin MB, Nakamura K, Islam MJ, Yamagishi H, Miura N
    • Organizer
      The 7^<th> TAKAO international symposium on the etiology and morphogenesis of congenital heart disease
    • Place of Presentation
      Tokyo
    • Year and Date
      2013-07-13
    • Related Report
      2013 Final Research Report
  • [Presentation] アフリカツメが得る次胚形成における遺伝子発現?その22013

    • Author(s)
      Sato E, Onuma Y, Fujie M, Adati N, Uezato T, Miura N, Ito Y
    • Organizer
      第46回日本発生生物学会
    • Place of Presentation
      松江
    • Year and Date
      2013-05-29
    • Related Report
      2013 Final Research Report
  • [Presentation] C型肝炎ウイルスの感染機構の解析2013

    • Author(s)
      Islam M、則武秀尚、三浦直行
    • Organizer
      第65回日本細胞生物学会大会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] C型肝炎ウイルスの感染機構の解析2013

    • Author(s)
      Islam, Mohammed Johirul
    • Organizer
      第65回日本細胞生物学会大会
    • Place of Presentation
      ウインク愛知
    • Related Report
      2013 Annual Research Report
  • [Presentation] コンディショナルFoxc2ノックアウトマウスを用いた大血管形成の分子機構の解明2013

    • Author(s)
      三浦直行
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] アフリカツメが得る次胚形成における遺伝子発現―その22013

    • Author(s)
      佐藤英二
    • Organizer
      第46回日本発生生物学会
    • Place of Presentation
      くにびきメッセ(松江)
    • Related Report
      2013 Annual Research Report
  • [Presentation] コンディショナルFoxc2ノックアウトマウスを用いた心臓形成遺伝子のドメイン解析2012

    • Author(s)
      木村航、Uddin MKH、山岸敬幸、三浦直行
    • Organizer
      第11回心臓血管発生研究会
    • Place of Presentation
      磐梯熱海
    • Year and Date
      2012-10-14
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Remarks]

    • URL

      http://www2.hama-med.ac.jp/w1a/bio2/index-j.html

    • Related Report
      2013 Final Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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