Molecular pathogenesis and therapeutic strategy of congenitalmuscular dystrophies with glycosylation defects

• Project/Area Number: 19790232
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Osaka University
• Principal Investigator: KANAGAWA Motoi Osaka University, 特任助教(常勤), 特任助教(常勤) (00448044)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,480,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥180,000); Fiscal Year 2008: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2007: ¥2,700,000 (Direct Cost: ¥2,700,000)
• Keywords: 糖鎖異常 / 筋ジストロフィー / 糖鎖治療 / ジストログリカン / フクチン / 分子病態学 / モデルマウス

Research Abstract

本研究目的は、福山型筋ジストロフィー(FCMD)の発症機序を理解し、治療戦略を構築することである。FCMDでは、ジストログリカンという糖タンパク質に糖鎖修飾異常が生じており、これが発症に関与すると考えられている。本研究では、独自に作出したFCMDモデルマウスの病態・生化学解析を行った。その結果、糖鎖異常を完全に回復させる必要はなく、部分的な回復のみで病態の軽減・抑制につながる、という新概念を提唱するに至った。更に、糖鎖異常の解消手段として、FCMD原因遺伝子のフクチン、あるいは、糖鎖増強作用を持つLARGEを対象とした遺伝子治療が効果的であることも示された。

Research Products

• [Journal Article] Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy. (2009)
  • Author(s): Kanagawa, M., Nishimoto, A., Chiyonobu, T., Takeda, S., Miyagoe-Suzuki,Y., Wang, F., Fujikake, N., Taniguchi, M., Lu, Z., Tachikawa, M., Nagai, Y., Tashiro, F., Miyazaki, J., Tajima, Y., Takeda, S., Endo, T., Kobayashi, K., Campbell, K.P., Toda, T.
  • Journal Title: Hum. Mol. Genet. 18 Pages: 621-631
  • Peer Reviewed
• [Journal Article] Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy (2009)
  • Author(s): Motoi Kanagawa
  • Journal Title: Human Molecular Genetics 18 Pages: 621-631
  • Peer Reviewed
• [Journal Article] Reduced expression of sarcospan in muscles of Fukuyama congenital muscular dystrophy. (2008)
  • Author(s): Wakayama, Y., Inoue, M., Kojima, H., Yamashita, S., Shibuya, S., Jimi, T., Hara, H., Matsuzaki, Y., Oniki, H., Kanagawa, M., Kobayashi, K., Toda, T.
  • Journal Title: Histol. Histopathol. 23 Pages: 1425-1438
  • Peer Reviewed
• [Presentation] Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy (2009)
  • Author(s): Kanagawa, M., Nishimoto, A., Chiyonobu, T., Takeda, S., Miyagoe-Suzuki, Y., Wang, F., Taniguchi, M., Lu, Z., Tachikawa, M., Tajima, Y., Takeda, S., Endo, T., Kobayashi, K., Campbell, K.P., Toda, T.
  • Organizer: Clinical and Translational Research on Cancer : Glycomics Applications and The 2^<nd> Seminar on Functional Glycomics for Young Investigators
  • Place of Presentation: 鳥羽
• [Presentation] ジストログリカンの糖鎖異常を示すモデルマウスを用いた先天性筋ジストロフィーの病態解析と治療戦略の構築 (2008)
  • Author(s): 金川 基、西本明美、千代延友裕、武田 聖、戸田達史
  • Organizer: Biochemistry and Molecular Biology 2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] ジストログリカンの糖鎖異常を示すモデルマウスを用いた先天性筋ジストロフィーの病態解析と治療戦略の構築 (2008)
  • Author(s): 金川基
  • Organizer: 日本分子生物学会年会日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] Molecular Pathogenesis and Therapeutic Strategy for Congenital Muscular Dystrophies Caused by Abnormal Giycosylation of Dystroglycan (2008)
  • Author(s): 金川基
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-18
• [Presentation] Molecular Pathogenesis and Therapeutic Strategy for Congenital Muscular Dystrophies Caused by Abnormal Glycosylation of Dystroglycan (2008)
  • Author(s): Kanagawa, M., Nishimoto, A., Chiyonobu T., Toda, T.
  • Organizer: 28th Japanese Carbohydrate Symposium
  • Place of Presentation: つくば
• [Presentation] Generation of a model mouse for Fukuyama congenital muscular dystrophy carrying a retrotransposal insertion in the 3' UTR in the fukutin gene (2008)
  • Author(s): Kanagawa, M., Nishimoto, A., Chiyonobu, T., Takeda, S., Toda, T.
  • Organizer: The Third New Directions in Skeletal Muscle Biology Meeting
  • Place of Presentation: New Orleans
• [Presentation] Generation of a model mouse for Fukuyama congenital muscular dystrophy carrying a retrotransposal insertion in the 3' UTR in the fukutin gene (2008)
  • Author(s): 金川基
  • Organizer: New Direction of Muscle Biology and Disease 2008
  • Place of Presentation: New Orleans
• [Presentation] Molecular interaction between fukutin and POMGnTl in the glycosylationpathway of alpha-dystroglycan (2007)
  • Author(s): 金川 基
  • Organizer: 第27回札幌がんセミナー
  • Place of Presentation: 札幌
  • Year and Date: 2007-07-13
• [Book] Experimental Glycoscience (Taniguchi, N., Suzuki, A., Ito, Y., Narimatsu, H., Kawasaki, T., and Hase, S. eds.) (2008)
  • Author(s): Kanagawa, M., and Toda, T. Fukutin and Fukuyama congenital muscular dystrophy.
  • Publisher: Springer, Tokyo
• [Book] Glycoscience Lab Manual (2008)
  • Author(s): 金川 基
  • Publisher: Elsevier Science Publishers
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/Pub/clgene/www/menu.html
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/clgene/www/menu.html