Generation and characterization of transgenic mice expressing mutated WWP1 gene responsible for chicken muscular dystrophy

• Project/Area Number: 21500384
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurophysiology and muscle physiology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: IMAMURA Michihiro 独立行政法人国立精神・神経医療研究センター, 神経研究所遺伝子疾患治療研究部, 室長 (80221787)
• Co-Investigator(Kenkyū-buntansha): MANNEN Hideyuki 神戸大学, 大学院・農学研究科, 教授 (20263395)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 酵素 / 細胞組織 / 遺伝子 / 実験動物 / 筋ジストロフィー

Research Abstract

The WWP1 gene was identified as a promising candidate responsible for chicken muscular dystrophy, which encodes a E3 ubiquitin protein ligase. Dystrophy chicken has a missense mutation in the gene causes one amino acid change in the molecule. To gain insight into molecular mechanism of the muscular dystrophy, we generated transgenic(Tg) mice expressing the same mutated WWP1 as found in dystrophy chicken. Tg mice showed a small number of necrotic and regenerating fibers in the hind limb muscle. Moreover, vacuoles were often found in aged Tg mice. Whereas, aberrant glycosylation ofα-dystroglycan was not shown in Tg muscle despite of a report with dystrophy chicken.

Research Products

• [Journal Article] (2010)
  • Author(s): Matsumoto H, Sasazaki S, Fujiwara A, Ichihara N, Kikuchi T, Mannen H
  • Journal Title: Comp Biochem Physiol A Mol Integr Physiol Volume: vol.157 Issue: 1 Pages: 68-72
  • DOI: 10.1016/j.cbpa.2010.04.019
  • Peer Reviewed
• [Journal Article] Accumulation of caveolin-3 protein is limited in damaged muscle in chicken muscular dystrophy. (2010)
  • Author(s): Matsumoto H, Sasazaki S, Fujiwara A, Ichihara N, Kikuchi T, Mannen H.
  • Journal Title: Comparative Biochemistry and Physiology-Part A : Molecular & Integrative Physiology Volume: 157 Pages: 68-72
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): Masuda-Hirata M, Suzuki A, Amano Y, Yamashita K, Ide M, Yamanaka T, Sakai M, Imamura M, Ohno S
  • Journal Title: Genes to Cells Volume: vol.14 Issue: 7 Pages: 835-850
  • DOI: 10.1111/j.1365-2443.2009.01315.x
  • Peer Reviewed
• [Journal Article] Expression Pattern of WWP1 in Muscular Dystrophic and Normal Chickens (2009)
  • Author(s): Matsumoto H, Maruse H, Sasazaki S, Fujiwara A, Takeda S, Ichihara N, Kikuchi T, Mukai F, Mannen H
  • Journal Title: The Journal of Poultry Science Volume: 46 Issue: 2 Pages: 95-99
  • DOI: 10.2141/jpsa.46.95
  • NAID: 130004446291
  • ISSN: 1346-7395, 1349-0486
  • Peer Reviewed
• [Journal Article] Intracellular polarity protein PAR-1 regulates extracellular laminin assembly by regulating the dystroglycan complex (2009)
  • Author(s): Masuda-Hirata M, Suzuki A, Amano Y, Yamashita K, Ide M, Yamanaka T, Sakai M, Imamura M, Ohno S
  • Journal Title: Genes to Cells 14 Pages: 835-850
  • Peer Reviewed
• [Journal Article] Expression Pattern of WWP1 in Muscular Dystrophic and Normal Chickens (2009)
  • Author(s): Matsumoto H, Maruse H, Sasazaki S, Fujiwara A, Takeda S, Ichihara N, Kikuchi T, Mukai F, Mannen H
  • Journal Title: The Journal of Poultry Science 46 Pages: 95-99
  • NAID: 10024799250
  • Peer Reviewed
• [Presentation] Analysis of Expression of WWP1 protein in Mouse Normal Tissues (2011)
  • Author(s): IMAMURA, Michihiro
  • Organizer: 51^<st> American Society for Cell Biology Annual Meeting
  • Place of Presentation: Colorado Convention Center, Denver, USA
  • Year and Date: 2011-12-04
• [Presentation] Effect of a Point Mutation in the WWP1 Gene Associated with Chicken Muscular Dystrophy on Mouse Muscle Expressing Mutated WWP1 Transgene (2011)
  • Author(s): 今村道博
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 北海道大学クラーク会館,北海道
  • Year and Date: 2011-06-28
• [Presentation] (2011)
  • Author(s): Imamura M, Takeda S
  • Organizer: 51^<th> Annual Meeting American Society for Cell Biology
  • Place of Presentation: Denver(U. S. A.)
• [Presentation] Generation of transgenic mouse expressing mutated wwp1 gene responsible for chicken muscular dystrophy. (2010)
  • Author(s): Imamura M, Matsumoto H, Inaba Y, Mannen H, Takeda S
  • Organizer: American Society for Cell Biology
  • Place of Presentation: Pennsylvania Convention Center, Philadelphia, PA, USA
  • Year and Date: 2010-12-14
• [Presentation] (2010)
  • Author(s): Imamura M, Takeda S
  • Organizer: 50^<th> Annual Meeting American Society for Cell Biology
  • Place of Presentation: Philadelphia(U. S. A.)
• [Presentation] (2010)
  • Author(s): 今村道博,松本大和,稲葉由美,万年英之,武田伸一
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 札幌
• [Presentation] Searching for loss of imprinting of theε-sarcoglycan gene in the cells of ε-sarcoglycan partial knockout mice (2009)
  • Author(s): Imamura M, Takeda S
  • Organizer: American Society for Cell Biology
  • Place of Presentation: San Diego Convention Center San Diego, CA, USA
  • Year and Date: 2009-12-08
• [Presentation] (2009)
  • Author(s): Imamura M, Takeda S
  • Organizer: 49^<th> Annual Meeting American Society for Cell Biology
  • Place of Presentation: San Diego(U. S. A.)