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DEVELOPMENT OF CLONE TRANSGENIC RABBITS FOR THE STUDY OF ATHEROSCLEROSIS

Research Project

Project/Area Number 11557016
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Human pathology
Research InstitutionSAGA MEDICAL SCHOOL (2000-2001)
University of Tsukuba (1999)

Principal Investigator

WATANABE Teruo  SAGA MEDICAL SCHOOL, VICE PRESIDENT, 副学長 (40037396)

Co-Investigator(Kenkyū-buntansha) HONDA Kazuo  YAMANOUCHI TSUKUBA RESEARCH INSTITUTE, PRESIDENT, 筑波研究所, 薬理研究所長
FAN Jianglin  UNIVERSITY OF TSUKUBA, INSTITUTE OF BASIC MEDICAL SCIENCES, LECTURER, 基礎医学系, 講師 (60272192)
KIMOTO Masao  SAGA MED SCHOOL, IMMUNOLOY, PROFESSOR, 医学部, 教授 (40153225)
井出 良浩  筑波大学, 基礎医学系, 講師 (70258606)
長崎 比呂央  明治大学, 農学部, 助教授 (50318664)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2000: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1999: ¥6,000,000 (Direct Cost: ¥6,000,000)
Keywordsclone / animal cloning / hypercholesterolemia / atherosclerosis / animal models / transgenic rabbit / transgene / lipoproteins / 遺伝子操作 / ウサギ / 体細胞クローン / 細胞核融合
Research Abstract

Transgenic rabbits are widely used as both bioreactors for the production of therapeutic proteins and human disease models in many biomedical fields. In attempt to generate transgenic rabbits by nuclear transfer technique, we performed the initial trial in making clone rabbits using somatic cells from transgenic rabbits and herewith we have optimized several factors that may be involved in the success of nuclear transfer procedures such as culture media, fusion and activation conditions and other related factors. Both electric fusion and piezo methods were used in this study. Although the generation of clone rabbits using somatic cells is still in immature state, it seems that compared to other species (goat, sheep, cow, mouse and pig), rabbit cloning using somatic cell nuclear transfer is rather complicated and a lot of procedures need to be refined before we can succeed in making cloned rabbits. In the second part of the study, we investigated transgenic rabbits expressing human apo(a) in terms of Lp(a) atherogenicity after cholesterol diet feeding. We found that transgenic rabbits developed greater atherosclerosis in aorta and coronary arteries than did control rabbits.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Ichikawa, T., Unoki, H., Sun, H., Shimoyamada, H., Shikama, T., Watanabe, T., Fan, J.: "Lipoprotein(a) promotes smooth muscle cell proliferation and dedifferentiation in atherosclerotic lesions of human apo(a) transgenic rabbits"Am J. Pathol.. 160. 227-236 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fan, J., Unoki, H., Kojima, N., Sun, H., Shimoyamada, H., Watanabe, T.: "Overexpression of lipoprotein lipase in transgenic rabbits inhibits diet-induced hypercholesterolemia and atherosclerosis"J. Biol. Chem.. 276. 40071-40079 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fan, J., Sun, H., Unoki, H., Shiomi, M., Watanabe, T.: "Enhanced atherosclerosis in Lp(a) WHHL transgenic rabbits"Ann New York Acad. Sci.. 947. 362-365 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fan, J., Shimoyamada, H., Sun, H., Marcovina, S., Watanabe, T.: "Transgenic rabbits expressing human apolipoprotein(a) develop enhanced atherosclerotic lesions in response to a cholesterol-rich diet"Arterioscl. Thromb. Vascul. Biol.. 21. 88-94 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wu, L., Tanimoto, A., Murata, Y., Fan, J., Sasaguri, Y., Watanabe, T.: "Induction of human metalloproteinase-12 gene transcritional activity by GM-CSF requires the AP-1 binding site in human U937 monocytic cells"Biochem. Biophys. Res. Commun.. 285. 300-307 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iwasa, S., Fan, J., Miyauchi, T., Watanabe, T.: "Blokade of endothelin receptors reduces diet-induced hypercholesterolemia and atherosclerosis in apoE-deficient mice"Pathobiology. 69. 1-10 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichikawa, T. Unoki, H.,l Sun, H., Shimoyamada, H., Shikama, T., Watanabe, T., Fan, J.: "Lipoprotein(a) promotes smooth muscle cell proliferation and dedifferentiation in atherosclerotic lesions of human apo(a) transgenic rabbits"Am. J. Pathol.. 160. 227-236 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fan, J., Unoki, H., Kojima, N., Sun, H., Shimoyamada, H., Deng, H., Yamada, N., Watanabe, T.: "Overexpression of lipoprotein lipase in transgenic rabbits inhibits diet-induced hypercholesterolemia and atherosclerosis"J. Biol. Chem.. 276. 40071-40079 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fan, J., Sun, H., Unoki, H., Shiomi, M.,Watanabe, T.: "Enhanced atherosclerosis in Lp(a) WHHL transgenic rabbits"Ann New York Acid. Sci.. 947. 362-365 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wu, L., Tanimoto, A., Murata, Y., fan, J., Sasaguri, Y., Watanabe, T: "Induction of human metalloproteinase-12 gene transcritional activity by GM-CSF requires the AP-1 binding site in human U937 monocytic cells"Bikochem. Biophys. Res. Commun.. 285. 300-307 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iwassa, S., Fan, J., Miyauchi, T., Watanabe, T.: "Biokade of endothelin receptors reduces diet-induced hypercholesterolemia and atherosclerosis in apoE-deficient mice"Pathobiology. 69. 1-10 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fan, J., Shimoyamada, H., Sun, H., Marcovina, S., Honda, K., Watanabe, T.: "Transgenic rabbits expressing hunman apolipoprotein(a) develop enhanced altherosclerotic lesions in response to a cholesterol-rich diet"Arterioscl. Thromb. Vascul. Biol.. 21. 88-94 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fan, J. and Watanabe, T.: "Cholesterol-fed and transgenic rabbit models for the study of atherosclerosis"J. Atheroscl. Thromb.. 7. 26-32 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fan, J. and Watanabe, T.: "Transgenic rabbits expressing human apolipoprotein(a)"J. Atheroscl. Thromb.. 7. 8-13 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fan, J., and Watanabe, T.: "Human apo(a) transgenicd rabbit, as a useful model for the study of human Lp(a)"Ann New York Acad. Sci. 902. 347-351 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fan, J. Challah, M. Shimoyamada,k H., Shiomi, M., Marcovina, S., Watanabe, T.: "Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein(a)"J. Lipid Res.. 41(6). 1004-1012 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fan, J., Challah, M. and Watanabe, T.: "Transgenic rabbit models for biomedical research, Current status, basic methods, and future perspectives"Pathol. Int.. 49. 583-594 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Araki, A., Fan, J., Challah, M. Bensadound, A., Yamada, N. and Watanabe, T.: "Human lipoprotein lipase transgenic rabbits"Cyhtotechnology. 31. 1-7 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] wu, L., Fan, J., Matsumoto, S., Watanabe, T.: "Induction and regulation of matrix metalloproteinase-12 by cytokines and CD40 signaling in monocyte/macrophages"Biochem Biophys Res Commun. 269. 808-815 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichikawa, T., Shimoyamada, H., Unoki, H., Sun, H., Shikama, T., Watanabe, T., Fan, J.: "Lipoprotein(a) promotes smooth muscle cell proliferation and dedifferentiation in atherosclerotic lesions of human apo(a) transgenic rabbits"Am J.Pathol.. 160. 227-236 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fan, J., Unoki, H., Kojima, N., Sun, H., Shimoyamada, H., Watanabe, T.: "Overexpression of lipoprotein lipase in transgenic rabbits inhibits diet-induced hypercholesterolemia and atherosclerosis"J.Biol.Chem.. 276. 40071-40079 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fan, J., Sun, H., Unoki, H., Shiomi, M., Watanabe, T.: "Enhanced atherosclerosis in Lp(a) WHHL transgenic rabbits"Ann New York Acad.Sci.. 947. 362-365 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fan, J., Shimoyamada, H., Sun, H., Marcovina, S., Watanabe, T.: "Transgenic rabbits expressing human apolipoprotein(a) develop enhanced atherosclerotic lesions in response to cholesterol-rich diet"Arteriosci.Thrormb.Vascul.Biol.. 21. 88-94 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Wu, L., Tanimoto, A., Murata, Y., Fan, J., Sasaguri, Y.Watanabe, T.: "Induction of human metalloproteinase-12 gene transcritional activity by GM-CSF requires the AP-1 binding site in human U937 monocytic cells"Biochem.Biophys.Res.Commun.. 285. 300-307 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwasa, S., Fan, J., Miyauchi, T., Watanabe, T: "Blokade of endothelin receptors reduces diet-induced hypercholesterolemia and atherosclerosis in apoE-deficient mice"Pathobiology. 69. 1-10 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fan,J.,Unoki,H.,Watanabe,T.: "Role of endothelin-1 in atherosclerosis"Ann New York Acad Sci. V. 84-94 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fan,J.,Challah,M.,Shimoyamada,H.,Watanabe,T.: "Transgenic rabbits expressing human apo(a) as a useful model for the study of lipoprotein(a)"Ann New York Acad Aci.. V. 347-351 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Araki,M.,Fan,J.,Watanabe,T.: "Transgenic rabbits expressing human lipoprotein lipase"Cytotechnology. 33. 93-99 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wu,L.,Fan,J.,Watanabe,T.: "Induction and regulation of matrix metalloproteinase-12 by cytokines and CD-40 signaling in monocyte/macrphages"Biochem Biophy Res Commun. 269. 808-815 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi,T.,Miyauchi,T.,Iwasa,S.,Fan,J.,Nagata,M.,Watanabe,T.: "Corresponding distributions of increased endothelin-B receptor expression and increase endothelin-1 in the aorta of apoE-deficient mice with advanced atherosclerosis"Pathol Int. 50. 929-936 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fan,J.,Challah,M.,Shimoyamada,H.,Marcovina,S.,Watanabe,T.: "Defects of LDL receptor in transgenic WHHL rabbits lead to a marked accumulation of plasma lipoprotein(a)"J Lipid Res. 41. 1004-1012 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fan,J, and Watanabe,T: "Human apo(a) transgenic rabbit, as auseful model for the syudy of human Lp(a)"Annual of New York Acad Sci. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fan,J, Iwasa,S, and Watanabe,T: "Role of endothelin in atherosclerosis"Annual of New York Acad Sci. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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