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GENERATION AND APPLICATION OF THE MODEL MICE WHICH SHOW RESISTANCE TO RENAL CARCINOGENESIS

Research Project

Project/Area Number 08557089
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Urology
Research InstitutionAKITA UNIVERSITY

Principal Investigator

MIURA Naoyuki  AKITA UNIV,SCH MED,ASSOC PROF, 医学部, 助教授 (40165965)

Co-Investigator(Kenkyū-buntansha) YOSHIDA Nobuaki  UNIV TOKYO,INST MED SCI,PROF, 医科学研究所, 教授 (10250341)
TERADA Kunihiko  AKITA UNIV,SCH MED,ASSIST PROF, 医学部, 講師 (60197796)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥11,500,000 (Direct Cost: ¥11,500,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1996: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsTORANSGENIC MICE / CHEMICAL CARCINOGENESIS / RB PROTEN / KIDNEY CANCER / LIVER CANCER / TRANSGENE / HNF1 / トランスジェニックス / 腎臓 / 肝臓 / 肝切除 / 癌抑制性遺伝子 / Rb遺伝子 / 腎臓癌
Research Abstract

We have generated the HNF1 -Rb transgenic mice in which the human Rb CDNA is regulated under the 9kbp of HNF1 (hepatocyte nudear factor 1) promoter. They showed no apparent differences compared to the wild mice and they can transmit the transgene to their offspring. The numbers of the Rb transgene were 11.0 copies per haploid for line A and 4.2 copies per haploid for line B.The weights of kidney and liver in the Rb transgenic mice were not different from the control mice.
Next we treated the mice with Iron Nitrotriacetate intraperitoneally for 3 months for kidney carcinogenesis and with diethylnitrosamine intraperitoneally and phenobarbital orally for 8 months for liver carcinogenesis. Control mice developed kidney carcinomas and liver carcinomas. The Rb transgenic mice, line A and line B, did not develop liver carcinoma and also showed smaller number of nodules than control mice, However, the Rb transgenic mice develop kidney carcinomas as frequently as control mice. In order to explain the differences between the effects of Rb transgene, we investigated the expression pattern of the Rb trausgene using the coinjected FNF1 -LacZ gene. The results showed that the Rb transgene was expressed in all hepatocytes, but in a small number of renal tubular cells. The expression profile is in good consistency with the resistance to chemical carcinogenesis.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Yasui, O.: "Isolation of oval cells from Long-Evans Cinnamon on rats and their transformation into hepatocytes in vivo in the rat liver." Hepatology. 25. 329-334 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Miura, N.: "Isolation of the mouse(MFH-1)and human(FKHL14)Mesenchyme Fork Head-1 genes reveals conservation of their gene and protein structures." Genomics. 41. 489-492 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iida, K.: "Essential roles of the winged h elix transcription factor MFH-1 in aor tic arch patterning and skeletogenesis." Development. 124. 4627-4638 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Terada, K.: "Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WNDcDNA." J.Biol.Chem.273. 1815-1820 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawarada, Y.: "Antibody against single-stranded DNA useful for detecting apoptotic cells recognizes hexadeoxynucleotides with various base sequences." J.Biochem.123. 492-498 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Furumoto, T.: "Notochordo dependent expression of MFH-1 and Pax-1 cooperates to maintain the proliferation of sclerotome during the vertebral column development." Dev.Biol.印刷中.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasui, O., Miura, N., Terada, K., Kawarada, Y., Koyama, K., and Sugiyama, T.: "Isolation of oval cells from Long-Evans Cinnamon rats and their transformation into hepatocytes in vivo in the rat liver." Hepatoloty. 25. 329-334 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Miura, N., Iida, K., Kakinuma, H., Yang, X-L., and Sugiyama, T.: "Isolation of the mouse (MFH-1) and human (FKHL14) Mesenchyme Fork Head-1 genes reveals conservation of their gene and protein structures." Genomics. 41. 489-492 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iida, K., Koseki, H., Kakinuma, H., Kato, N., Mizutani-Koseki, Y., Ohuchi, H., Yoshioka, H., Noji, S., Kawamura, K., Kataoka, Y., Ueno, F., Taniguchi, M., Yoshida, N., Sugiyama, T., and Miura, N.: "Essential roles of the winged helix transcription factor MFH-1 in aortic arch patterning and skeletogenesis." Development. 124. 4627-4638 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Terada, K., Nakako, T., Yang, X-L., Iida, M., Aiba, N., Minamiya, Y., Nakai, M., Sakaki, T., Miura, N., and Sugiyama, T.: "Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA" J.Biol.Chem.273. 1815-1820 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawarada, Y., Miura, N., and Sugiyama, T.: "Antibody against single-stranded DNA useful for detecting apoptotic cells recognizes hexadeoxynucleotides with various base sequences." J.Biochem. 123. 492-498 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Furumoto, T., Miura, N., Akasaka, T., Mizutani-Koseki, Y., Sudo, H., Fukuda, K., Maekawa, M., Yuasa, S., Fu, Y., Moriya, H., Taniguchi, M., Imai, K., Dahl, E., Balling, R., Pavlova, M., Gossler, A., and Koseki, H.: "Notochordo dependent expression of MFH-1 and Pax-1 cooperates to maintain the proliferation of sclerotome during the vertebral column development." Dev.Biol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Terada,K.: "Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA." J.Biol.Chem.273. 1815-1820 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawarada,Y.: "Antibody against single-stranded DNA useful for detecting apoptotic cells recognizes hexadeoxynucleotides with various base sequences." J.Biochem.123. 492-498 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kobayashi,S.: "Detection od DNA fragmentation in human breast cancer tissue by an antibody specific to single-stranded DNA." Breast Cancer. 5. 47-52 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miura,N.: "Mouse forkhead (winged helix) gene LUN encode a transactivator that acts in the lung." Genomics. 50. 346-356 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Schilsky,M.L.: "Copper resistant human hepatoma mutant cell lines without metallothioneion induction overexpress ATP7B" Hepatology. 28. 1347-1356 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Furumoto,T.: "Notochordo dependent expression of MFH-1 and Pax-1 cooperates to maintain the proliferation of sclerotome during the vertebral column development." Dev.Biol.(印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasui,O.: "Isolation of oval cells from Long-Evans Cinnamon rats and their transformation into hepatocytes in vivo in the rat liver." Hepatology. 25. 329-334 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miura,N.: "Isolation of the mouse (MFH-1) and human (FKHL14) Mesenchyme Fork Head-1 genes reveals conservation of their gene and protein structures." Genomics. 41. 489-492 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yang,X-L.: "Two forms of Wilson disease proteins produced by alternative splicing are localized in distinct cellular compartments." Biochem.J.326. 897-902 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Iida,K.: "Essential roles of the winged helix transcription factor MFH-1 in aortic arch patterning and skeletogenesis." Development. 124. 4627-4638 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Terada,K.: "Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA." J.Biol.Chem.273. 1815-1820 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miura,N.: "Mouse forkhead (winged helix) gene LUN encode a transactivator that acts in the lung." Genomics. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] 三浦直行: "ノックアウトマウス・データブック" 中山書店, 564 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Masuda,Y: "Platelet-derived growth factor B-chain homodimer suppressing a tonic-clonic convulsion of seizure-prone El mouse." Biochim. Biophys. Res. Commun.223. 60-63 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yasui,O: "Isolation of oval cells from Long-Evans Cinnamon rats and their transformation into hepatocytes in vivo in the rat liver." Hepatology. 25. 329-334 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirasawa,F.: "The effect of silver administration on the biosynthesis and molecular properties of rat ceruloplasmin." Biochim. Biophys. Acta. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Kuhara,M.: "Enhancing effect of a congenital disorder in methionine metabolism on the development of spontaneous hepatitis and hepatoma in LEC rats." J.Trace Elem.Exp.Med.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Miura,N.: "Isolation of the mouse and human MFH-1 (Mesenchyme Fork Head-1) genes reveals conservation of their gene and protein structures." Genomics. (in press).

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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