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Development of transgenic rabbits as models for atherosclerotic research

Research Project

Project/Area Number 08557017
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Human pathology
Research InstitutionUniversity of Tsukuba

Principal Investigator

WATANABE Teruo  Univ.of Tsukuba Basic Med.Sci.Professor, 基礎医学系, 教授 (40037396)

Co-Investigator(Kenkyū-buntansha) YAGAMI Kenichi  Univ.of Tsukuba Exp.Animal Center, Professor, 動物実験センター, 教授 (40166476)
TOMIOKA Kenichi  Yamanouchi Pharmac.Comp.Assoc.Head, 創薬研究本部, 副所長
SHIMOKAWA Tatsuro  Univ.of Tsukuba Basic Med.Sci.Assis.Prof., 基礎医学系, 助教授 (50170999)
FAN Jianglin  Univ.of Tsukuba Basic Med.Sci.Lecture, 基礎医学系, 講師 (60272192)
富岡 健一  山之内製薬, 創薬研究本部・第2創薬研究所, 副所長
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 1998: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1997: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1996: ¥6,500,000 (Direct Cost: ¥6,500,000)
KeywordsTransgenic Animals / Lipoproteins / Hypercholesterolemia / Rabbit / Apoproteins / Gene expression / Cloning / トランスジェニックウサギ / レムナント / 冠状動脈硬化 / 危険因子 / リボ蛋白 / リボ蛋白(a)
Research Abstract

For the study of atheroslerosis, we have successfully generated transgenic rabbits expressing either human apolipoprotein(a) [Lp(a)] or lipoprotein lipase (LPL) at the end of 1998.
Apo(a) transgenic rabbits :
Totally, 93 pups were obtained after transplantation into foster mothers. 11 rabbits were found to have transgene integrated into their genome. 3 transgenic rabbits soon after birth and 5 transgenic rabbits show no detectable expression of apo(a) in the plasma. 3 transgenic rabbit lines have been established ; A01 line has 1.8mg/dl, A46 line has 3.4 mg/dI, and A47 line has 4.5 mg/dl of apo(a) in the plasma. A10 line has been bred into F1 and F2 and the following results were obtained. Human apo(a) mRNA expression was mainly found in the liver and kidney. Plasma apo(a), in transgenic rabbits showed a similar mobility to human Lp(a) at pre-beta position. In the plasma of transgenic rabbits, unlike the plasma of transgenic mice, about 80% of the apo(a) was covalently associated with rabbit apo-B and was contained in the fractions with density 1.02-1.10 g/ml, indicating the formation of Lp(a). These results suggest that transgenic rabbits expressing human apo(a) exhibit efficient assembly of Lp(a) and can be used as an animal model for the study of human Lp(a). Now, we have started to breed more F1 for the study of atherosclerosis by feeding cholesterol-rich diet.
LPL transgenic rabbits :
Until now, we have produced 3 LPL transgenic rabbits under the control of chicken b-actin promoter and 4 LPL transgenic rabbits under the control of scavenger receptor promoter. Characterization of these transgenic rabbits are currently underway.

Report

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

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 渡辺照男、范 江霖: "遺伝子操作による病態モデルの開発、トランスジェニックウサギ" ファルマシア. 32. 50-54 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 范 江霖、渡辺照男: "トランスジェニックウサギ、動脈硬化+高脂血症研究ストラテジー" 細胞工学別冊 山田信博、佐藤靖史監修. 秀潤社. 447-449 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsumoto,S.,Katoh,M.,Sato,S.,Watanabe,T: "Identification of Soluble type of membrane-type matrix met alloproteinase-3 formed by alternative spliced mRNA." Biochem.Biopys.Acta. 1354. 159-170 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 渡辺 照男: "動脈硬化研究のためのトランスジェニックウサギ-疾患モデル動物の作製-" 医学の歩み. 182. 396-400 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Araki M,Fan J and Watanabe T: "Immunohisto chemical localization of lipoprotein lipase and apolipoprotein E in human atherosclerotic lesions." Acta.Histochem.Cytochem. 32(6). 485-492 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fan J,Araki M.WuL,et al.and Watanabe T: "Assembly of lipoprotein (a) in transgenic rabbits expressing human apolipoprotein (a)." Biochem Biophys Res Commun255. 255. 639-644 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsumoto, S., Katoh, M., Saito, S., Watanabe, T., Masuho, Y.: "Identification of soluble type of membrane-type matrix metalloproteinase-3 formed by alternative spliced mRNA,Biochem." Biochem Biophys Acta. 1354. 159-170 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Araki M,Fan J and Watanabe T: "Immunohistochemical localization of lipoprotein lipase and apolipoprotein E in human an atherosclerotic lesions." Acta Histochem Cytochem. 32. 485-492 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fan J,Araki M,Wu L,Challah M,Shimoyamada H,Lawn R,Kakuta H,Shikama H and Watanabe T: "Assembly of lipoprotein (a) in trnasgenic rabbits expressing human apolipoprotein (a)." Biochem Biophys Res Commun. 255. 639-644 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Araki M,Fan J,Challah M,Bensadoun A,Yamada N,Kakuta H,Shikama H and Watanabe T: "Transgenic rabbits expressing human lipoprotein lipase." Cytotechnology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fan J.Challah M and Watanabe T: "Transgenic rabbit models for biomedical research. Current status, basic methods and future perspective." Pathol Internat. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fan J,Araki M,Wu L,et al.: "Transgenic rabbits expressing human apolipoprotein(a)" Circulation. Suppl.370 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Araki M,Fan J.Watanabe,T.: "Immunohistochemical localization of lipoprotein lipase and apolipoprotein(a)in human atherosclesetic lesions" Acta Histochemica Cytochemica. 31(6). 485-492 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fan J,Araki M,Wu L,et al.: "Assembly of lipoprotein(a)in transgenic rabbits expressing human apolipoprotein(a)" Biochemical and Biophysical Research Communications. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 渡辺 照男: "動脈硬化研究のためのトランスジェニックウサギ -疾患モデル動物の作製-" 医学のあゆみ. 182. 396-400 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 渡辺照男、范,江霖: "遺伝子操作による病態モデルの開発。トランスジェニックウサギ" ファルマシア. 32. 51-54 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 范,江霖、渡辺照男: "トランスジェニックウサギ。動脈硬化+高脂血症ストラテジー。" 細胞工学別冊 山田信博、佐藤靖史監修 秀潤社. 447-449 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 范,江霖: "Transgenicrabbit models. Recent insights into the roles of hepatic lipase and apolipoprotein E in atherosclerosis.21GC03:Ther.Res." 17. 809-818 (1996)

    • Related Report
      1996 Annual Research Report

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

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