Development of disease model pigs suitable for diabetic complications research

2013 Fiscal Year Final Research Report

• Project/Area Number: 23500505
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Meiji 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
• 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.

Research Products

• [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): Satoshi Hara, Kazuhiro Umeyama, Takashi Yokoo, Hiroshi Nagashima, Michio Nagata
  • Journal Title: PLoS One Volume: Vol. 9 Pages: e92219
  • DOI: 10.1371/journal.pone.0092219.eCollection2014
  • Peer Reviewed
• [Journal Article] Production of diabetic offspring using cryopreserved epididymal sperm by in vitro fertilization and intrafallopian insemination techniques in transgenic pigs (2013)
  • Author(s): Kazuhiro Umeyama, Kasumi Honda, Hitomi Matsunari, Kazuaki Nakano, Tatsuro Hidaka, Keito Sekiguchi, Hironori Mochizuki, Yasuhiro Takeuchi, Tsukasa Fujiwara, Masahito Watanabe, Masaki Nagaya, Hiroshi Nagashima
  • Journal Title: J Reprod Dev Volume: Vol. 59 Pages: 599-603
  • DOI: 10.1262/jrd.2013-069
  • 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 HUMANS (2014)
  • 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)
  • Year and Date: 20140514-17
• [Presentation] Diabetic retinopathy in transgenic pigs with induced diabetes mellitus (2014)
  • 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)
  • Year and Date: 20140504-08
• [Presentation] Evolution of Glomerular Nodular Lesions in Diabetic Pigs Carrying a Dominant-Negative Mutant Hepatocyte Nuclear Factor 1-Alpha (2013)
  • 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)
  • Year and Date: 20131105-10
• [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)
  • Year and Date: 20130912-14
• [Presentation] PATHOLOGICAL ANALYSIS OF GLOMERULAR NODULAR LESION IN DIABETIC PIGS CARRYING A DOMINANT-NEGATIVE MUTANT HEPATOCYTE NUCLEAR FACTOR 1-ALPHA (2013)
  • 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)
  • Year and Date: 20130531-0604
• [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)
  • Year and Date: 20130510-12
• [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)
  • Year and Date: 20120524-26
• [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
• [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)
  • Year and Date: 20111203-04
• [Presentation] Development of genetically modified pigs suitable for diabetes and its complications research (2011)
  • 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)
  • Year and Date: 20110717-19
• [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)
  • Year and Date: 20110525-27
• [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
• [Book] The Minipig in Biomedical Research. Chapter 28, Creation and Conservation of Genetically Modified Pigs: Applications to Genetic Disease Model and Xenotransplantation (2011)
  • Author(s): Hiroshi Nagashima, Hitomi Matsunari, Kazuhiro Umeyama
  • Total Pages: 415-430
  • Publisher: CRC Press