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

• Project/Area Number: 24659603
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Hamamatsu 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: ¥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)
• Keywords: C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.

Research Products

• [Journal Article] Control of retinoid levels by CYP26B1 is important for lymphatic vascular development in the mouse embryo (2014)
  • 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
• [Journal Article] TGFa, c-MYC, mutated CTNNB1 and their combinations act distinctly on the Hep3B tumors in nude mice (2014)
  • 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
• [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
  • Peer Reviewed
• [Journal Article] FOXC2 expression links epitherial-mesenchymal transition and stem cell properties in breast cancer (2013)
  • 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
• [Journal Article] Generation and characterization of Tbx1-AmCyan1 transgenic reporter mouse line that selectively labels developing thymus primordium (2013)
  • Author(s): Kimura W, Sharkar MTK, Sultana N, Islam MJ, Uezato T, Miura N
  • Journal Title: Transgenic Res Volume: 22 Pages: 659-666
• [Journal Article] Foxc2 induces Wnt4 and Bmp4 expression during muscle regeneration and osteogenesis (2013)
  • 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
• [Journal Article] Phosphorylation regulates FOXC2-mediated transcription in lymphatic endothelial cells (2013)
  • 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
• [Journal Article] Baicalin and scutellarin are proteasome inhibitors that specifically target chymotrypsin-like catalytic activity (2013)
  • Author(s): Wu Y-X, Sato E, Kimura W, Miura N
  • Journal Title: Phytother Res Volume: 27 Pages: 1362-1367
• [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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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 genes (2012)
  • 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
• [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
• [Journal Article] Mechanotransduction, PROX1 and FOXC2 cooperate to control connexin 37 and calcineurin during lymphatic valve formation (2012)
  • 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
• [Journal Article] Semaphorin 3A, Neuropilin-1, and PlexinA1 are required for lymphatic valve formation (2012)
  • 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
• [Journal Article] The regulation of endogenous retinoic acid level through CYP26B1 is reqired 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 Pages: 1744-1756
• [Journal Article] Liver tumor formation by a mutant retinoblastoma protein in the transgenic mice is caused by an up-regulation of c-Myc target genes (2012)
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Presentation] TGFα, c-MYC, mutated CTNNB1 and their combinations act distinctly on the Hep3B tumors in nude mice (2014)
  • 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
• [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
• [Presentation] The loss of Foxc2 in the outflow tract links the interrupted arch in the conditional Foxc2 knockout mouse (2013)
  • 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
• [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2 (2013)
  • 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
• [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
• [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
• [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
  • 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２ (2013)
  • 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）
• [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
• [Remarks]
  • URL: http://www2.hama-med.ac.jp/w1a/bio2/index-j.html