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Production of gene-modified pig of next-generation model for Alzheimer's disase

Research Project

Project/Area Number 16H05176
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKagoshima University

Principal Investigator

Tanimoto Akihide  鹿児島大学, 医歯学域医学系, 教授 (10217151)

Co-Investigator(Kenkyū-buntansha) 佐藤 正宏  鹿児島大学, 総合科学域総合研究学系, 教授 (30287099)
三好 和睦  鹿児島大学, 農水産獣医学域農学系, 教授 (70363611)
川口 博明  鹿児島大学, 医歯学域医学系, 准教授 (60325777)
三浦 直樹  鹿児島大学, 農水産獣医学域獣医学系, 准教授 (80508036)
堀内 正久  鹿児島大学, 医歯学域医学系, 教授 (50264403)
小澤 政之  鹿児島大学, 医歯学域医学系, 教授 (90136854)
Research Collaborator NOGUCHI michiko  
OHTAKE masayoshi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords動物モデル / マイクロミニブタ / 遺伝子改変 / クローン動物 / アルツハイマー病 / クローンブタ / 体細胞核移植 / 受精卵採取 / 受精卵遺伝子改変 / マイクロミニピッグ / クローン / 疾患モデル動物 / 遺伝子改変動物 / 体細胞クローン
Outline of Final Research Achievements

To understand the pathogenesis of lifestyle disease and disorder in higher brain function, a development of proper animal model, which is similar to human pathogenesis, is necessary. In addition to the anatomy and physiology, pig is very comparable to human in its life style, food habit and brain function. We have already established a human type atherosclerosis model using microminipigs by feeding high fat diet. On the other hand, Alzheimer's diseases are increasing in number of patients. To clarify the pathogenesis and development of a novel drug for Alzheimer's disease is urgent task in Japan. Our research that are going to produce a gene-modified microminipig having Alzheimer's pathology would contribute to overcome the disease. By the present study, the understanding and accumulation of our fundamental knowledge for reproductive physiology, embryo transfer and clone technology to prepare the Alzheimer's disease-reproducing gene-modified microminipig extensively proceeded.

Academic Significance and Societal Importance of the Research Achievements

ブタの知能はイヌ程度であり、遺伝子改変マイクロミニピッグの作製により、ヒトに近似したアルツハイマー病の病態モデルの開発が成功すれば、高次脳機能障害のモデル動物として、マウス・ラットよりもヒトに近い脳機能評価のモデルになり、機能性食品や薬剤の新規開発のため強力なツールとなる。イヌ、ブタなどの大型動物では、近親交配による近交退化が見られ、マウスやラットとは異なり近交系の作出が困難とされている。マイクロミニピッグでもその可能性は否定できないが、クローン技術を背景にして遺伝子改変動物を作製することで、ヒトの病態を再現する遺伝子の多様性を維持したままのマイクロミニピッグの利用が可能となる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (17 results)

All 2018 2017 2016

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 6 results)

  • [Journal Article] Timing of CRISPR/Cas9-related mRNA microinjection after activation as an important factor affecting genome editing efficiency in porcine oocytes2018

    • Author(s)
      Sato M, Maeda K, Koriyama M, Inada E, Saitoh I, Ohtsuka M, Nakamura S, Sakurai, T, Watanabe S, Miyoshi K
    • Journal Title

      Theriogenology

      Volume: 108 Pages: 29-38

    • DOI

      10.1016/j.theriogenology.2017.11.030

    • NAID

      120007099790

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Combinational Use of CRISPR/Cas9 and Targeted Toxin Technology Enables Efficient Isolation of Bi-Allelic Knockout Non-Human Mammalian Clones2018

    • Author(s)
      Watanabe Satoshi、Sakurai Takayuki、Nakamura Shingo、Miyoshi Kazuchika、Sato Masahiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 19 Issue: 4 Pages: 1075-1075

    • DOI

      10.3390/ijms19041075

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Dietary and Lighting Conditions on Diurnal Locomotor Activity and Body Temperature in Microminipigs.2018

    • Author(s)
      Takeishi K, Kawaguchi H, Akioka K, Noguchi M, Arimura E, Abe M, Ushikai M, Okita S, Tanimoto A, Horiuchi M.
    • Journal Title

      In Vivo

      Volume: 32 Issue: 1 Pages: 55-62

    • DOI

      10.21873/invivo.11204

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient Generation of Somatic Cell Nuclear Transfer-Competent Porcine Cells with Mutated Alleles at Multiple Target Loci by Using CRISPR/Cas9 Combined with Targeted Toxin-Based Selection System.2017

    • Author(s)
      Sato M, Miyoshi K, Nakamura S, Ohtsuka M, Sakurai T, Watanabe S, Kawaguchi H, Tanimoto A.
    • Journal Title

      Int J Mol Sci

      Volume: 18 Issue: 12 Pages: 2610-2610

    • DOI

      10.3390/ijms18122610

    • NAID

      120007099791

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Corpus luteum regression induced by prostaglandin F2α in Microminipigs during the normal estrous cycle.2017

    • Author(s)
      Noguchi M, Hirata M, Kawaguchi H, Tanimoto A
    • Journal Title

      In Vivo

      Volume: 31 Issue: 6 Pages: 1097-1101

    • DOI

      10.21873/invivo.11175

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypertension alters the endothelial-dependent biphasic response of bradykinin in isolated Microminipig basilar artery.2017

    • Author(s)
      Zahorul Islam M, Kawaguchi H, Miura N, Miyoshi N, Yamazaki-Himeno E, Shiraishi M, Miyamoto A, Tanimoto A.
    • Journal Title

      Microvascular Research

      Volume: 114 Pages: 52-57

    • DOI

      10.1016/j.mvr.2017.06.001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cholic Acid Enhances Visceral Adiposity, Atherosclerosis and Nonalcoholic Fatty Liver Disease in Microminipigs2017

    • Author(s)
      Yamada S, Kawaguchi H, Yamada T, Guo X, Matsuo K, Hamada T, Miura N, Tasaki T, Tanimoto A.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 24 Issue: 11 Pages: 1150-1166

    • DOI

      10.5551/jat.39909

    • NAID

      130006191597

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Birth of Cloned Microminipigs Derived from Somatic Cell Nuclear Transfer Embryos that have been Transiently Treated with Valproic Acid.2016

    • Author(s)
      Miyoshi K, Maeda K, Akioka K, Sato M, Kawaguchi H, Tanimoto A
    • Journal Title

      Cellular Reprogramming

      Volume: 6 Issue: 6 Pages: 390-400

    • DOI

      10.1089/cell.2016.0025

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Estrus synchronization in microminipig using estradiol dipropionate and prostaglandin F<sub>2α</sub>2016

    • Author(s)
      Nogcuhi M., Ikedo T., Kawaguchi H., Tanimoto A
    • Journal Title

      Journal of Reproduction and Development

      Volume: 62 Issue: 4 Pages: 373-378

    • DOI

      10.1262/jrd.2015-169

    • NAID

      130005406792

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 細胞障害の制御とその破綻による病態発生:自然炎症メカニズムと粥状動脈硬化症2018

    • Author(s)
      谷本昭英
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] The world’s smallest Microminipigs and its clone: A novel atherosclerosis-prone miniature pigs2018

    • Author(s)
      谷本 昭英、川口 博明、佐藤 正宏、三好 和睦、大竹 正剛、三浦 直樹、野口 倫子
    • Organizer
      第19回 Atherosclerosis and Biolipid Conference
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] マイクロミニピッグにおける体細胞クローニング2018

    • Author(s)
      三好 和睦
    • Organizer
      第20回応用薬理シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] The world’s smallest Microminipigs and its clone2017

    • Author(s)
      Akihide Tanimoto, Hiroaki Kawaguchi, Kazuchima Miyoshi, Masayoshi Otake
    • Organizer
      7th International Congress on Rabbit Biotechnology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Pathology of atheroscelrosis in microminipig2016

    • Author(s)
      谷本昭英、川口博明
    • Organizer
      第43 回日本毒性学会学術年会
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] マイクロミニピッグを用いた医学研究の現状2016

    • Author(s)
      谷本昭英、川口博明、三好和睦、大竹 正剛
    • Organizer
      第48回日本動脈硬化学会総会・学術集会
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] piggyBac遺伝子導入系により複数遺伝子が同時導入されたブタ細胞は核移植後のクローン胚の発生を保証する2016

    • Author(s)
      佐藤正宏,前田昂亮,郡山実優,稲田絵美,齋藤一誠,大塚正人,中村伸吾,桜井敬之,渡部聡,三好和睦
    • Organizer
      第109回日本繁殖生物学会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 医用ブタにおける遺伝子組換え動物作製の実際とその可能性について2016

    • Author(s)
      佐藤正宏、渡部聡、大塚正人
    • Organizer
      第50回日本実験動物技術者協会総会
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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