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Development of disease model pigs suitable for diabetic complications research

Research Project

Project/Area Number 23500505
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory animal science
Research InstitutionMeiji University

Principal Investigator

NAGASHIMA Hiroshi  明治大学, 農学部, 教授 (50318664)

Co-Investigator(Kenkyū-buntansha) UMEYAMA Kazuhiro  明治大学, 研究 知財戦略機構, 准教授 (70342699)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsブタ / 遺伝子組換え動物 / 病態モデル動物 / 糖尿病 / 合併症 / 糖尿病腎症 / 糖尿病網膜症
Research Abstract

This study aimed at identifying the characteristics of transgenic(tg) pigs as a research model for diabetes and its complications. Tg pigs carrying a mutant gene, human HNF-1alpha(P291fsinsC), responsible for maturity-onset diabetes of the young type 3, were obtained by in vitro fertilization using the cryopreserved sperm from tg founder. The tg pigs maintained a high blood glucose level(>200mg/dl). The oral glucose tolerance test showed that the recovery of the blood sugar levels of the pigs was significantly delayed compared with non-tg pigs. The hypoplasia of the islets of Langerhans was confirmed by the histopathological image of the tg pigs' pancreas. The histopathological image of the tg pigs' kidney showed a nodular lesion typical of diabetic nephropathy in humans. Also, retinal hemorrhages and cotton-wool spots were confirmed in the tg pigs. These data demonstrate that the tg pigs is a promising model for research into diabetets and its complications.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (28 results)

All 2014 2013 2012 2011 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (24 results) (of which Invited: 1 results) Book (2 results)

  • [Journal Article] Diffuse glomerular nodular lesions in diabetic pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha, an inheritant diabetic gene in humans.2014

    • Author(s)
      Hara S, Umeyama K, Yokoo T, Nagashima H, Nagata M.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 3 Pages: e92219-e92219

    • DOI

      10.1371/journal.pone.0092219

    • NAID

      120007130512

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Production of Diabetic Offspring Using Cryopreserved Epididymal Sperm by <i>In Vitro</i> Fertilization and Intrafallopian Insemination Techniques in Transgenic Pigs2013

    • Author(s)
      Umeyama K, Honda K, Matsunari H, Nakano K, Hidaka T, Sekiguchi K, Mochizuki H, Takeuchi Y, Fujiwara T, Watanabe M, Nagaya M, Nagashima H.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 59 Issue: 6 Pages: 599-603

    • DOI

      10.1262/jrd.2013-069

    • NAID

      130003361059

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Presentation] DIFFUSE GLOMERULAR NODULAR LESIONS IN DIABETIC PIGS CARRYING A DOMINANT-NEGATIVE MUTANT HEPATOCYTE NUCLEAR FACTOR ONE-ALPHA, AN INHERITANT DIABETIC GENE IN HUMANS2014

    • Author(s)
      Satoshi Hara, Kazuhiro Umeyama, Takashi Yokoo, Hiroshi Nagashima, Michio Nagata
    • Organizer
      The 14th Asian Pacific Congress of Nephrology 2014
    • Place of Presentation
      Shinagawa Prince Hotel(Minato-ku, Tokyo, Japan)
    • Related Report
      2013 Final Research Report
  • [Presentation] Diabetic retinopathy in transgenic pigs with induced diabetes mellitus2014

    • Author(s)
      Masami Nakajima, Akiko Ishimori, Kazuhiro Umeyama, Hiroshi Nagashima
    • Organizer
      The Association for Research in Vision and Ophthalmology 2014 Annual Meeting
    • Place of Presentation
      Orange County Convention Center (Orlando, Florida, USA)
    • Related Report
      2013 Final Research Report
  • [Presentation] Diabetic retinopathy in transgenic pigs with induced diabetes mellitus2014

    • Author(s)
      Masami Nakajima, Akiko Ishimori, Kazuhiro Umeyama, Hiroshi Nagashima
    • Organizer
      The Association for Research in Vision and Ophthalmology 2014 Annual Meeting
    • Place of Presentation
      Florida, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Diffuse glomerular nodular lesions in diabetic pigs carrying a dominant-negative mutant hepatocyte nuclear factor one-alpha, aninheritant diabetic gene in humans2014

    • Author(s)
      Satoshi Hara, Kazuhiro Umeyama, Takashi Yokoo, Hiroshi Nagashima, Michio Nagata
    • Organizer
      The 14th Asian Pacific Congress of Nephrology 2014
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] Evolution of Glomerular Nodular Lesions in Diabetic Pigs Carrying a Dominant-Negative Mutant Hepatocyte Nuclear Factor 1-Alpha2013

    • Author(s)
      Satoshi Hara, Kazuhiro Umeyama, Takashi Yokoo, Hiroshi Nagashima, Michio Nagata
    • Organizer
      The Kidney Week 2013
    • Place of Presentation
      Georgia World Convention Center (Atlanta, Georgia, USA)
    • Related Report
      2013 Final Research Report
  • [Presentation] PATHOLOGICAL ANALYSIS OF GLOMERULAR NODULAR LESION IN DIABETIC PIGS CARRYING A DOMINANT-NEGATIVE MUTANT HEPATOCYTE NUCLEAR FACTOR 1-ALPHA2013

    • Author(s)
      Satoshi Hara, Takashi Yokoo, Kazuhiro Umeyama, Hiroshi Nagashima, Michio Nagata
    • Organizer
      International Society of Nephrology, World Congress of Neprology 2013
    • Place of Presentation
      The Hong Kong Convention and Exhibition Centre(Hong Kong, China)
    • Related Report
      2013 Final Research Report
  • [Presentation] ガラス化保存された体外成熟/体外受精胚を用いた糖尿病モデル遺伝子改変ブタの作出2013

    • Author(s)
      松村幸奈, 前原美樹, 本田香澄, 林田豪太, 倉本桃子, 中野和明, 松成ひとみ, 小林美里奈, 内倉鮎子, 浅野吉則, 渡邊將人, 梅山一大, 長屋昌樹, 長嶋比呂志
    • Organizer
      第106回日本繁殖生物学会大会
    • Place of Presentation
      東京農工大学(東京都府中市)
    • Related Report
      2013 Final Research Report
  • [Presentation] Dominat-negative 変異型 hepatocyte nuclear factor 1α(HNF1α)導入糖尿病ブタにおける糸球体結節性病変の解析2013

    • Author(s)
      原怜史, 横尾隆, 梅山一大, 長嶋比呂志, 長田道夫
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム(東京都中央区)
    • Related Report
      2013 Final Research Report
  • [Presentation] Dominat-negative変異型hepatocyte nuclear factor 1α(HNF1α)導入糖尿病ブタにおける糸球体結節性病変の解析2013

    • Author(s)
      原怜史、横尾隆、梅山一大、長嶋比呂志、長田道夫
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] ガラス化保存された体外成熟/体外受精胚を用いた糖尿病モデル遺伝子改変ブタの作出2013

    • Author(s)
      松村幸奈,前原美樹,本田香澄,林田豪太,倉本桃子,中野和明,松成ひとみ,小林美里奈,内倉鮎子,浅野吉則,渡邊將人,梅山一大,長屋昌樹,長嶋比呂志
    • Organizer
      第106回日本繁殖生物学会大会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Pathological analysis of glomerular nodular lesion n diabetic pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha2013

    • Author(s)
      Satoshi Hara, Takashi Yokoo, Kazuhiro Umeyama, Hiroshi Nagashima, Michio Nagata.
    • Organizer
      International Society of Nephrology, World Congress of Neprology 2013
    • Place of Presentation
      Honk Kong, China
    • Related Report
      2013 Annual Research Report
  • [Presentation] Evolution of Glomerular Nodular Lesions in Diabetic Pigs Carrying a Dominant-Negative Mutant Hepatocyte Nuclear Factor 1-Alpha2013

    • Author(s)
      Satoshi Hara, Kazuhiro Umeyama, Takashi Yokoo, Hiroshi Nagashima, Michio Nagata
    • Organizer
      The Kidney Week 2013
    • Place of Presentation
      Georgia, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 遺伝子改変ブタ・クローンブタのトランスレーショナルリサーチへの応用2012

    • Author(s)
      長嶋比呂志, 松成ひとみ, 渡邊将人, 梅山一大, 長屋昌樹
    • Organizer
      JALAM (日本実験動物医学会)シンポジウム
    • Place of Presentation
      別府国際コンベンションセンター(大分県別府市)
    • Year and Date
      2012-05-23
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖尿病発症遺伝子改変ブタによるNonalcoholic fatty liver disease(NAFLD)病変の作出2012

    • Author(s)
      梅山一大, 渡邊將人, 本田香澄, 竹内靖浩, 中野和明, 松成ひとみ, 横尾隆, 長嶋比呂志
    • Organizer
      第59回日本実験動物学会総会
    • Place of Presentation
      別府国際コンベンションセンター(大分県別府市)
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖尿病発症遺伝子改変ブタによるNonalcoholic fatty liver disease(NAFLD)病変の作出2012

    • Author(s)
      梅山一大、渡邊將人、本田香澄、竹内靖浩、中野和明、松成ひとみ、横尾隆、長嶋比呂志
    • Organizer
      第59回日本実験動物学会総会
    • Place of Presentation
      ビーコンプラザ(別府)
    • Related Report
      2012 Research-status Report
  • [Presentation] 糖尿病モデル・変異型ヒト HNF-1α遺伝子を導入したトランスジェニックブタの病態解析2011

    • Author(s)
      梅山一大, 渡邊將人, 松成ひとみ, 中野和明, 藤原主, 日高龍路, 竹内靖浩, 本田香澄, 望月寛徳, 関口渓人, 長嶋比呂志
    • Organizer
      第25回日本糖尿病・肥満動物学会
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2011-11-05
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖尿病発症遺伝子改変ブタによる結節性病変を有した腎病変の作出2011

    • Author(s)
      梅山一大, 渡邊將人, 松成ひとみ, 中野和明, 竹内靖浩, 本田香澄, 長田道夫, 横尾隆, 長嶋比呂志
    • Organizer
      第23回日本糖尿病性腎症研究会
    • Place of Presentation
      ベルサール神田(東京千代田区)
    • Related Report
      2013 Final Research Report
  • [Presentation] Development of genetically modified pigs suitable for diabetes and its complications research2011

    • Author(s)
      Kazuhiro Umeyama, Masahito Watanabe, Hitomi Matsunari, Kazuaki Nakano, Yasuhiro Takeuchi, Kasumi Honda, Takashi Yokoo, Hiroshi Nagashima
    • Organizer
      Swine in Biomedical Research 2011
    • Place of Presentation
      Holiday Inn Chicago Mart Plaza(Chicago, IL, USA)
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖尿病合併症に適した遺伝子改変ブタの開発2011

    • Author(s)
      梅山一大, 渡邊將人, 松成ひとみ, 中野和明, 竹内靖浩, 本田香澄, 横尾隆, 長嶋比呂志
    • Organizer
      第58回日本実験動物学会
    • Place of Presentation
      タワーホール船掘(東京江戸川区)
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖尿病合併症に適した遺伝子改変ブタの開発2011

    • Author(s)
      梅山一大、渡邊將人、松成ひとみ、中野和明、竹内靖浩、本田香澄、横尾隆、長嶋比呂志
    • Organizer
      日本実験動物学会
    • Place of Presentation
      タワーホール船掘(東京)
    • Related Report
      2011 Research-status Report
  • [Presentation] Development of genetically modified pigs suitable for diabetes and its complications research2011

    • Author(s)
      K. Umeyama, M. Watanabe, H. Matsunari, K. Nakano, Y. Takeuchi, K. Honda, T. Yokoo, H. Nagashima
    • Organizer
      Swine in Biomedical Research 2011
    • Place of Presentation
      Holiday Inn Chicago Mart Plaza(Chicago, IL)
    • Related Report
      2011 Research-status Report
  • [Presentation] 糖尿病モデル・変異型ヒトHNF-1α遺伝子を導入したトランスジェニックブタの病態解析2011

    • Author(s)
      梅山一大、渡邊將人、松成ひとみ、中野和明、藤原主、日高龍路、竹内靖浩、本田香澄、望月寛徳、関口渓人、長嶋比呂志
    • Organizer
      日本糖尿病・肥満動物学会
    • Place of Presentation
      東京大学工学部武田先端知ビル(東京)
    • Related Report
      2011 Research-status Report
  • [Presentation] 糖尿病発症遺伝子改変ブタによる結節性病変を有した腎病変の作出2011

    • Author(s)
      梅山一大、渡邊將人、松成ひとみ、中野和明、竹内靖浩、本田香澄、長田道夫、横尾隆、長嶋比呂志
    • Organizer
      日本糖尿病性腎症研究会
    • Place of Presentation
      ベルサール神田(東京)
    • Related Report
      2011 Research-status Report
  • [Presentation] 遺伝子改変ブタ・クローンブタのトランスレーショナルリサーチへの応用

    • Author(s)
      長嶋比呂志、松成ひとみ、渡邊将人、梅山一大、長屋昌樹
    • Organizer
      JALAM(日本実験動物医学会)シンポジウム
    • Place of Presentation
      ビーコンプラザ(別府)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Book] The Minipig in Biomedical Research. Chapter 28, Creation and Conservation of Genetically Modified Pigs: Applications to Genetic Disease Model and Xenotransplantation2012

    • Author(s)
      Hiroshi Nagashima, Hitomi Matsunari, Kazuhiro Umeyama
    • Publisher
      CRC Press
    • Related Report
      2011 Research-status Report
  • [Book] The Minipig in Biomedical Research. Chapter 28, Creation and Conservation of Genetically Modified Pigs: Applications to Genetic Disease Model and Xenotransplantation2011

    • Author(s)
      Hiroshi Nagashima, Hitomi Matsunari, Kazuhiro Umeyama
    • Publisher
      CRC Press
    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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