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Generation and application of gene knock-out rabbits for the study of atherosclerosis

Research Project

Project/Area Number 21659078
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionUniversity of Yamanashi

Principal Investigator

FAN Jianglin  山梨大学, 大学院・医学工学総合研究部, 教授 (60272192)

Co-Investigator(Kenkyū-buntansha) KOIKE Tomonari  山梨大学, 大学院・医学工学総合研究部, 助教 (40432158)
SHIBATA Nobumitsu  山梨大学, 大学院・医学工学総合研究部, 医学研究員 (40452130)
Co-Investigator(Renkei-kenkyūsha) TEZUKA Hideo  山梨大学, 総合分析実験センター, 准教授 (70155456)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,370,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2009: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsCETP / 核移植 / クローン / HDL / 動脈硬化 / ノックアウト / 遺伝子導入 / ウサギ / 動脈硬化モデル / 高脂血症 / トランスジェニック / モデル動物
Research Abstract

It is essential to use genetically modified animals for the elucidation of disease-related gene functions and therapeutic candidate proteins in vivo. In this field, transgenic mice are widely used in the medical research. However, due to the differences between mouse and human in lipid metabolism and cardiovascular system, it is considered that mice are not suitable for the research of lipid metabolism and cardiovascular disease of humans. In the current study, we attempted to establish a somatic cell line with cholesteryl ester transfer protein deficiency and then, using nuclear transfer technology, to make cholesteryl ester transfer protein knock-out rabbits.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (49 results)

All 2012 2011 2010 2009 Other

All Journal Article (27 results) (of which Peer Reviewed: 27 results) Presentation (15 results) Book (2 results) Remarks (4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Endothelial lipase mediates hdl levels in normal and hyperlipidemic rabbits2012

    • Author(s)
      Zhang J, Yu Y, Nakamura K, Koike T, Waqar AB, Zhang X, Liu E, Nishijima K, Kitajima S, Shiomi M, Qi Z, Yu J, Graham MJ, Crooke RM, Ishida T, Hirata K, Hurt-Camejo E, Chen YE, Fan J
    • Journal Title

      J Atheroscler Thromb

      Volume: 19 Pages: 213-226

    • NAID

      130004444589

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] C-reactive protein is associated with the progression of acute embolic stroke in rabbit model2012

    • Author(s)
      Yu Q, Lin Y, Yang P, Wang Y, Zhao S, Yang P, Fan J, Liu E
    • Journal Title

      J Thromb Thrombolysis

      Volume: 33 Pages: 301-307

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] C-reactive protein levels are associated with the progression of atherosclerotic lesions in rabbits2012

    • Author(s)
      Yu Q, Li Y, Wang Y, Zhao S, Yang P, Chen Y, Fan J, Liu E
    • Journal Title

      Histol Histopathol

      Volume: 27 Pages: 529-535

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-dose rosiglitazone is pro-atherogenic in cholesterol-fed rabbits2012

    • Author(s)
      Wang Y, Cheng F, Chen Y, S. Z, Yu Q, Fan J, Liu E
    • Journal Title

      Atherosclerosis

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] C-reactive protein levels are associated with the progression of atherosclerotic lesions in rabbits2012

    • Author(s)
      Yu Q, et al
    • Journal Title

      Histol Histopatol

      Volume: 27 Pages: 529-535

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-dose rosiglitazone is pro-atherogenic in cholesterol-fed rabbits2012

    • Author(s)
      Wang Y, et al
    • Journal Title

      Atherosclerosis

      Volume: 222 Issue: 1 Pages: 292-294

    • DOI

      10.1016/j.atherosclerosis.2012.01.048

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Temporal and quantitative analysis of atherosclerotic lesions in diet-induced hypercholesterolemic rabbits2012

    • Author(s)
      Yu Q, et al
    • Journal Title

      J Biomed Biotechnol

      Volume: 2012 Pages: 1-7

    • DOI

      10.1155/2012/506159

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of human c-reactive protein on pathogenesis of features of the metabolic syndrome2011

    • Author(s)
      Pravenec M, Kajiya T, Zidek V, Landa V, Mlejnek P, Simakova M, Silhavy J, Malinska H, Oliyarnyk O, Kazdova L, Fan J, Wang J, Kurtz TW
    • Journal Title

      Hypertension

      Volume: 57 Pages: 731-737

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human c-reactive protein enhances thrombus formation after neointimal balloon injury in transgenic rabbits2011

    • Author(s)
      Matsuda S, Yamashita A, Sato Y, Kitajima S, Koike T, Sugita C, Moriguchi-Goto S, Hatakeyama K, Takahashi M, Koshimoto C, Matsuura Y, Iwakiri T, Chen YE, Fan J, Asada Y
    • Journal Title

      J Thromb Haemost

      Volume: 9 Pages: 201-208

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Factors influencing the number of eggs recovered from rabbits superovulated with fsh or pmsg : Analysis of five years of data from 509 rabbits2011

    • Author(s)
      Kitajima S, Maeda T, Nishijima K, Morimoto M, Watanabe T, Fan J
    • Journal Title

      Scand. J. Lab. Anim. Sci

      Volume: 38 Pages: 169-174

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Perfluorooctane sulfonate impairs the cardiac development of a marine medaka(oryzias melastigma)2011

    • Author(s)
      Huang Q, Fang C, Wu X, Fan J, Dong S
    • Journal Title

      Aquat Toxicol

      Volume: 105 Pages: 71-77

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits expressing human apolipoprotein ciii2011

    • Author(s)
      Ding Y, Wang Y, Zhu H, Fan J, Yu L, Liu G, Liu E
    • Journal Title

      Transgenic Res

      Volume: 20 Pages: 867-875

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Perfluorooctane sulfonate impairs the cardiac development of a marine medaka (oryzias melastigma)2011

    • Author(s)
      Huang Q, et al
    • Journal Title

      Aquat Toxicol

      Volume: 105 Issue: 1-2 Pages: 71-77

    • DOI

      10.1016/j.aquatox.2011.05.012

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits expressing human apolipoprotein CIII2011

    • Author(s)
      Ding Y, et al
    • Journal Title

      Transgenic Res

      Volume: 20 Issue: 4 Pages: 867-875

    • DOI

      10.1007/s11248-010-9467-5

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits exDressing human apolipoprotein CIII.2011

    • Author(s)
      Ding Y
    • Journal Title

      Transgenic Res.

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Human C-Reactive Protein on Pathogenesis of Features of the Metabolic Syndrome.2011

    • Author(s)
      Pravenec M
    • Journal Title

      Hypertension

      Volume: 57 Pages: 731-737

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human C-reactive protein enhances thrombus formation after neaintimal balloon injury in transgenic rabbits.2011

    • Author(s)
      Matsuda S
    • Journal Title

      J Thromb Haemost.

      Volume: 9 Pages: 201-208

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A practical method for quantifying atherosclerotic lesions in rabbits2010

    • Author(s)
      Zhang C, Zheng H, Yu Q, Yang P, Li Y, Cheng F, Fan J, Liu E
    • Journal Title

      J Comp Pathol

      Volume: 142 Pages: 122-128

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-fat diet without excess calories induces metabolic disorders and enhances atherosclerosis in rabbits2010

    • Author(s)
      Waqar AB, Koike T, Yu Y, Inoue T, Aoki T, Liu E, Fan J
    • Journal Title

      Atherosclerosis

      Volume: 213 Pages: 148-155

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Letter by nakajima and saito regarding article,"human c-reactive protein does not promote atherosclerosis in transgenic rabbits"2010

    • Author(s)
      Nakajima K, Saito M, Fan J, Chen CY
    • Journal Title

      Circulation

      Volume: 122

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fat and cholesterol diet induced lipid metabolic disorders and insulin resistance in rabbit2009

    • Author(s)
      Zheng H, Zhang C, Yang W, Wang Y, Lin Y, Yang P, Yu Q, Fan J, Liu E
    • Journal Title

      Exp Clin Endocrinol Diabetes

      Volume: 117 Pages: 400-405

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endotoxin accelerates atherosclerosis independent of complement activation2009

    • Author(s)
      Reifenberg K, Lehr HA, Fan J, Koike T, Wiese E, Kupper I, Sagban TA, Schaefer SC, Zahringer U, Torzewski M, Lackner KJ, Bhakdi S
    • Journal Title

      Thromb Res

      Volume: 123 Pages: 653-658

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human c-reactive protein does not promote atherosclerosis in transgenic rabbits2009

    • Author(s)
      Koike T, Kitajima S, Yu Y, Nishijima K, Zhang J, Ozaki Y, Morimoto M, Watanabe T, Bhakdi S, Asada Y, Chen YE, Fan J
    • Journal Title

      Circulation

      Volume: 120 Pages: 2088-2094

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of human apoaii in transgenic rabbits leads to dyslipidemia : A new model for combined hyperlipidemia2009

    • Author(s)
      Koike T, Kitajima S, Yu Y, Li Y, Nishijima K, Liu E, Sun H, Waqar AB, Shibata N, Inoue T, Wang Y, Zhang B, Kobayashi J, Morimoto M, Saku K, Watanabe T, Fan J
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 29 Pages: 2047-2053

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Experssion of human apoAII in transgenic rabbits leads to dyslipidemia : a new model for combined hyperlipidemia.2009

    • Author(s)
      Koike T, et al.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 29

      Pages: 2047-2053

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human C-reactive protein does not promote atherosclerosis in transgenic rabbits.2009

    • Author(s)
      Koike T, et al.
    • Journal Title

      Circulation 120

      Pages: 2088-2094

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endotoxin accelerates atherosclerosis independent of complement activation.2009

    • Author(s)
      Reifenberg K, et al.
    • Journal Title

      Thromb Res. 123

      Pages: 653-658

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] ApoAII-rich HDLs have anti-inflammatory functions2012

    • Author(s)
      Koike T
    • Organizer
      XVI International Symposium on Atherosclerosis
    • Place of Presentation
      Sydney Convention and Exhibition Centre (Sydney)
    • Year and Date
      2012-03-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] The anti-atherogenic effects of probucol and cilostazol in cholesterol-fed rabbits2012

    • Author(s)
      Liu E
    • Organizer
      XVI International Symposium on Atherosclerosis
    • Place of Presentation
      Sydney Convention and Exhibition Centre (Sydney)
    • Year and Date
      2012-03-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] Transgenic rabbit models for the study of atherosclerosis2011

    • Author(s)
      Fan J
    • Organizer
      ISTH2011(第23回国際血栓止血学会)
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2011-07-23
    • Related Report
      2011 Final Research Report
  • [Presentation] Probucol has different anti-atherogenic effects compared to atorvastatin2011

    • Author(s)
      Niimi M
    • Organizer
      第43回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      ロイトン札幌(札幌市)
    • Year and Date
      2011-07-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Hypertriglyceridemia and delayed clearance of fat load in transgenic mice, rabbits and minipigs expressing human Apo CIII2011

    • Author(s)
      Liu G
    • Organizer
      第43回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      ロイトン札幌(札幌市)
    • Year and Date
      2011-07-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Apolipoprotein-AII plays an important role in lipid metabolism and atherosclerosis2011

    • Author(s)
      Koike T
    • Organizer
      第43回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      Hungarian Academy of Sciences (Budapest)
    • Year and Date
      2011-06-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] Nitro-oleic acid attenuates angiotensin II signaling pathway in vascular wall through inhibiting AT1 receptor and G-protein coupling2010

    • Author(s)
      Zhang J
    • Organizer
      第42回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      長良川国際会議場
    • Year and Date
      2010-07-15
    • Related Report
      2011 Final Research Report
  • [Presentation] Expression of Human ApoAIIin Transgenic Rabbits Leads to Dyslipidemia-A New Model for Combined Hyperlipidemia.2010

    • Author(s)
      Koike T
    • Organizer
      第42回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      長良川国際会議場(岐阜市)
    • Year and Date
      2010-07-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] 動脈硬化の発生におけるC反応性蛋白の役割:遺伝子改変ウサギ・モデルによる解析2010

    • Author(s)
      範江林
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Year and Date
      2010-04-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] 分子病理学研究所の最前線:動脈硬化の分子病態の解明及びトランスレーショナルリサーチへの挑戦2010

    • Author(s)
      範江林
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      京王プラザホテル
    • Year and Date
      2010-04-27
    • Related Report
      2011 Final Research Report
  • [Presentation] 動脈硬化の分子病態の解明及びトランスレーショナルリサーチへの挑戦2010

    • Author(s)
      範江林
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Year and Date
      2010-04-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] High-Fat-Diet-induced metabolic disorders enhances atherosclerosis2009

    • Author(s)
      Waqar AB
    • Organizer
      第41回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      海峡メッセ下関
    • Year and Date
      2009-07-17
    • Related Report
      2011 Final Research Report
  • [Presentation] Transgenic rabbits for translational research2009

    • Author(s)
      範江林
    • Organizer
      遺伝子改変ウサギ国際シンポジウム
    • Place of Presentation
      中国西安市
    • Year and Date
      2009-06-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] ウサギ採卵成績に影響を及ぼす要因の検討:過去5年間の採卵成績の解析2009

    • Author(s)
      北嶋修司
    • Organizer
      第56回日本実験動物学会総会
    • Place of Presentation
      大宮ソニックシティ
    • Year and Date
      2009-05-15
    • Related Report
      2011 Final Research Report
  • [Presentation] Transgenic rabbits expressing human c-reactive protein2009

    • Author(s)
      Koike T
    • Organizer
      ATVB Annual Conference 2009
    • Place of Presentation
      Omni Shoreham Hotel
    • Year and Date
      2009-04-30
    • Related Report
      2011 Final Research Report
  • [Book] Rabbit biotechnology transgenesis, cloning and models2009

    • Author(s)
      Houdebine L, Fan J
    • Total Pages
      136
    • Publisher
      Springer.
    • Related Report
      2011 Final Research Report
  • [Book] Rabbit Biotechnology : Rabbit genomics, transgenesis, cloning and models :2009

    • Author(s)
      Fan J, et al.
    • Total Pages
      140
    • Publisher
      Springer
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical_basic/pathol01/

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical_basic/pathol01/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical_basic/patho101/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical_basic/patho101/

    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] ヒトC反応性蛋白遺伝子導入ウサギ2009

    • Inventor(s)
      範江林, 他
    • Industrial Property Rights Holder
      国立大学法人佐賀大学、国立大学法人山梨大学、モアハウススクールオブメディシン
    • Patent Publication Number
      2010-284125
    • Filing Date
      2009-06-15
    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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