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Generation of mice in which the mouse hepatocytes are replaced with the human hepaocytes and its application

Research Project

Project/Area Number 19390347
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

MIURA Naoyuki  Hamamatsu University School of Medicine, 医学部, 教授 (40165965)

Co-Investigator(Kenkyū-buntansha) UEZATO Tadayoshi  浜松医科大学, 医学部, 准教授 (40115465)
SHINMURA Kazuya  浜松医科大学, 医学部, 准教授 (40321880)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2009: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Keywordsヒト肝細胞 / マウス / 肝細胞癌 / 化学発ガン / トランスジェニックマウス / 細胞移植 / 遺伝子導入 / レンチウィルス / 癌遺伝子 / 化学発癌 / レトロウィルス / トランスジェニックマエス / キメラマウス / 免疫不全マウス / アルプミン / 生体蛍光蛋白
Research Abstract

Alb-uPAトランスジェニックマウスに免疫不全scidマウスを交配し、Alb-uPAをトランスジーンにもつ免疫不全マウスを作製した。Alb-uPAホモ免疫不全マウスの生後3週目にヒト肝細胞を脾臓経由で移植すると4週後には、マウスの肝臓の50-100%がヒト肝細胞で置換されたマウスができた(肝臓ヒト化マウス)。肝臓ヒト化マウスに肝化学発癌剤であるジエチルニトロサミンとフェノバルビタールを投与すると、肝細胞腫(アデノーマ)が高頻度で発生した。腫瘍部のRNA解析では、c-Myc,FoxM1,c-Jun,c-Fos,Bmi1,Skp2mRNAが増加していることが判明した。

Report

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

    (41 results)

All 2010 2009 2008 2007 2006 Other

All Journal Article (19 results) (of which Peer Reviewed: 18 results) Presentation (16 results) Book (3 results) Remarks (3 results)

  • [Journal Article] A unique expression pattern of Tbx10 in the hindbrain as revealed by Tbx10(lacZ ) allele.2010

    • Author(s)
      Xue, X-D., Kimura W., Wang, B., Hikosaka, K., Itakura, T., Uezato, T., Matsuda, M., Koseki, H., Miura, N.
    • Journal Title

      Genesis 48

      Pages: 295-302

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of Prox1 targets during in vitro vascular differentiation from embryonic stem cells: functional roles of HoxD8 in lymphangenesis.2009

    • Author(s)
      Harada, K., Yamazaki, T., Iwata, C., Yoshimatsu, Y., Sase, H., Mishima, K., Morishita, Y., Hirashima, M., Oike, Y., Suda, T., Miura, N., Watabe, T., Miyazone, K.
    • Journal Title

      J. Cell Sci 122

      Pages: 3923-3930

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maruration defects resulting from geene-targeting of the PI3K regulatory isoforms p85a, p55a and p50a.2009

    • Author(s)
      Mouta-Bellum, C., Kirov, A., Micelli-Libby, L., Mancini, M.L., Petrova, T.V., Liaw, L., Prudovsky, I., Thorpe P.E., Miura, N., Cantley L.C., Alitaro, K., Fruman, D.A., Vary, C.P.H.
    • Journal Title

      Dev. Dyn 238

      Pages: 2690-2699

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fecal COX-2 plus MMP-7 mRNAassays as a marker for colorectalcancer screening.2009

    • Author(s)
      Takai, T., Kanaoka, S., Yoshida, K., Hamaya, Y., Ikuma, M., Miura, N., Sugimura, H., Kajimura, M., Hishida, A.
    • Journal Title

      Can. Epidemiol. Biomarkers Prev 18

      Pages: 1888-1893

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Integrin-a9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis.2009

    • Author(s)
      Bazigou, E., Xie, S., Chan, C., Weston, A., Miura, N., Sorokin, L., Adams, R., Muro, A.F., Sheppard, D., Makinen, T.
    • Journal Title

      Dev. Cell 17

      Pages: 175-186

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1.2009

    • Author(s)
      Norrmen, C., Cheng, J., Miura, N. Puolakkainen, P., Yla-Herttuala, S., Alitaro, K., Petrove, T.V.
    • Journal Title

      J. Cell Biol 185

      Pages: 439-457

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc12009

    • Author(s)
      Norrmen, C
    • Journal Title

      J.Cell Biol 185

      Pages: 439-457

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fecal COX-2 plus MMP-7 mRNAassays as a marker for colorectalcancer screening2009

    • Author(s)
      Takai, T.
    • Journal Title

      Can.Epidemiol.Biomarkers Prev 18

      Pages: 1888-1893

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Integrin-a9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis2009

    • Author(s)
      Bazigou, E.
    • Journal Title

      Dev.Cell 17

      Pages: 175-186

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutation analysis of FOXF2 in patients with disorders of sex development (DSD) in combination with cleft palate.2008

    • Author(s)
      Jochumsen, U., Werner, R., Miura, N., Richter-Unruh, A., Hiort, O., Holterhus, P-M.
    • Journal Title

      Sex. Dev 2

      Pages: 302-308

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The medaka FoxP2, a homologue of human language gene FOXP2, has a diverged structure and function.2008

    • Author(s)
      Itakura, T., Chandra, A., Yang, Z., Xue, X-D., Wang, B., Kimura, W., Hikosaka, K., Inohaya, K., Kudo, A., Uezato, T., Miura, N.
    • Journal Title

      J. Biochem 143

      Pages: 407-416

    • NAID

      10024908974

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutation analysis of FOXF2 in patients with disorders of sex development (DSD) in combination with cleft palate.2008

    • Author(s)
      Jochumsen, U.
    • Journal Title

      Sex Dev. 2

      Pages: 302-308

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The medaka FoxP2,a homologue of human language gene FOXP2,has adiverged structure and function2008

    • Author(s)
      Itakura, T.
    • Journal Title

      J.Biochem. 143

      Pages: 407-416

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 会話言語発達と遺伝子2008

    • Author(s)
      三浦 直行
    • Journal Title

      脳21 11

      Pages: 30-38

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Mesenchyme Forkhead 1(FOXC2)plays a key role in metastasis and is associated with aggressive basal-like breast cancers2007

    • Author(s)
      Mani, S.A.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 104

      Pages: 10069-10074

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The mouse forkhead gene Foxp2 modulates expression of the lung genes.

    • Author(s)
      Yang, Z., Hikosaka, K., Sharkar M.T.K., Tamakoshi, T., Chandra, A., wang, B., Itakura T., Xue, X-D., Uezato, T., Kimura W., Miura, N.
    • Journal Title

      Life Sciences (in press)

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc.

    • Author(s)
      Mani, S.A., Yang, J., Brooks, M., Schwaninger, G., Zhou, A., Miura, N., Kutok, J.L., Hartwell, K.H., Richardson, A.L., Weinberg, R.A.
    • Journal Title

      Natl. Acad. Sci. USA 104

      Pages: 10069-10074

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fecal COX-2 plus MMP-7 mRNAassays as a marker for colorectal cancer screening.

    • Author(s)
      Takai, T.
    • Journal Title

      Can. Epidemiol. Biomark. Prevent. (印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FOXC2 cotrols formation and maturation of lymphatic collecting vessels through cooperation with NFATc1.

    • Author(s)
      Norrmen, C.
    • Journal Title

      J. Cell Biol. (印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 心臓形成におけるIrx遺伝子の発現と役割2009

    • Author(s)
      三浦直行
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] 心臓形成におけるIrx遺伝子の発現と役割2009

    • Author(s)
      三浦直行, 待井将志, ニシャットサルタナ, モハマドシャーカー, 木村航
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜(ワークショップ)
    • Related Report
      2009 Final Research Report
  • [Presentation] マウスフォークヘッド遺伝子Foxp2は肺分化遺伝子の発現を制御する2009

    • Author(s)
      楊志, 彦坂圭介, 木村航, 上里忠良, 三浦直行
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Related Report
      2009 Final Research Report
  • [Presentation] マウスフォークヘッド遺伝子Foxp2は肺分化遺伝子の発現を制御する2009

    • Author(s)
      楊志, 彦坂圭介, 木村航, 上里忠良, 三浦直行
    • Organizer
      第61回日本細胞生物学会
    • Place of Presentation
      名古屋
    • Related Report
      2009 Final Research Report
  • [Presentation] 変異Rb蛋白を肝細胞に発現させると肝臓腫瘍を効率におこす2008

    • Author(s)
      王博, 福本和彦, 彦坂圭介, 三浦直行
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2009 Final Research Report 2008 Annual Research Report
  • [Presentation] The Tbx10 gene is expressed in the superior sulvatory nucleus in the medulla oblongata2008

    • Author(s)
      薛暁東, 木村航, 板倉達郎, 彦坂圭介, 三浦直行
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2009 Final Research Report
  • [Presentation] The medaka FoxP2, a homologue of human language gene FOXP2, has a diverged structure and function.2008

    • Author(s)
      板倉達郎, 楊志, 薛暁東, 木村航, 彦坂圭介, 三浦直行
    • Organizer
      第60回日本細胞生物学会
    • Place of Presentation
      横浜
    • Related Report
      2009 Final Research Report
  • [Presentation] Tbx10遺伝子は上部唾液分泌神経の有用なマーカーである2008

    • Author(s)
      薛暁東, 彦坂圭介, 木村航, 三浦直行
    • Organizer
      第41回日本発生生物学会
    • Place of Presentation
      徳島(ワークショップ)
    • Related Report
      2009 Final Research Report
  • [Presentation] メダカFoxP2タンパクの発現と機能について2007

    • Author(s)
      板倉達郎, Abhishek Chandra, 楊志, 三浦直行
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2009 Final Research Report
  • [Presentation] Characterization of the N-terminal signal sequence of Neurogenesin-1 and its role in early bone development2007

    • Author(s)
      Abhisheck Chandra, 板倉達郎, 三浦直行
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2009 Final Research Report
  • [Presentation] フォークヘッド遺伝子Foxp2の肺と消化管における発現と機能について2007

    • Author(s)
      楊志, Abhisheck Chandra, 板倉達郎, 三浦直行
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2009 Final Research Report
  • [Presentation] フォークヘッド遺伝子Foxj1の欠損により心臓大血管の左右は腹部臓器の左右とは独立に決定される2007

    • Author(s)
      三浦直行
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会
    • Place of Presentation
      横浜(ワークショップ)
    • Related Report
      2009 Final Research Report
  • [Presentation] Double axis formation in Xenopus laevis embryos by early perturbation just after insemination.2007

    • Author(s)
      佐藤英二, 柴田清, 藤江三千男, 呉一心, 上里忠良, 三浦直行
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2009 Final Research Report
  • [Presentation] Roles of the Foxj1 and Inv genes in the left-right determination of internal organs in mice2007

    • Author(s)
      Tomoki Tamakoshi, Tatsuo Itakura, Abhisheck Chandra, Tatsuhiko Yokoyama, Naoyuki Miura
    • Organizer
      第40回日本発生生物学会・第59回日本細胞生物学会
    • Place of Presentation
      福岡
    • Related Report
      2009 Final Research Report
  • [Presentation] The Foxf2 gene controls murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production.2007

    • Author(s)
      Tao Wang, Tomoki Tamakoshi, Peter Carlsson, Naoyuki Miura
    • Organizer
      第40回日本発生生物学会・第59回日本細胞生物学会
    • Place of Presentation
      福岡
    • Related Report
      2009 Final Research Report
  • [Presentation] フォークヘッド遺伝子Foxf2の腸管における上皮-間葉相互作用について2006

    • Author(s)
      王滔, 玉越智樹, 薛暁東, 三浦直行
    • Organizer
      日本分子生物学会フォーラム「分子生物学の未来」
    • Place of Presentation
      名古屋
    • Related Report
      2009 Final Research Report
  • [Book] Chapter 88 Introduction to Forkhead (Fox) Genes, in "Inborn Errors of Development: Molecular basis of clinical disorders of morphogenesis" 2nd edition, (Eds. Epstein, CJ, Erickson, RP, Wynshaw-Boris A)2008

    • Author(s)
      Miura, N., Xue, X-D., Itakura, T.
    • Publisher
      Oxford University Press
    • Related Report
      2009 Final Research Report
  • [Book] Inborn Errors of Development : Molecular basis of clinical disorders of morphogenesis, 2nd edition2008

    • Author(s)
      Miura, N.
    • Publisher
      Oxford University Press
    • Related Report
      2008 Annual Research Report
  • [Book] Inborn Errors of Development

    • Author(s)
      Miura, N.
    • Total Pages
      876
    • Publisher
      Oxford University Press(印刷中)
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2009 Final Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2007 Annual Research Report

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

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