Study on treatment of Duchenne muscular dystrophy by inducing exon skipping

• Project/Area Number: 19390284
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kobe University
• Principal Investigator: MATSUO Masafumi Kobe University, 大学院医学研究科, 教授 (10157266)
• Co-Investigator(Kenkyū-buntansha): TAKESHIMA Yasuhiro 神戸大学, 大学院医学研究科, 准教授 (40281141) ; YAGI Mariko 神戸大学, 大学院医学研究科, 助教 (60362787)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2007: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
• Keywords: 小児神経学 / ジストロフィン / リボゾーム / エクソンスキッピング / 治療

Research Abstract

私達のデュシェンヌ型筋ジストロフィー(DMD)の治療結果により、DMD骨格筋では「タンパク合成システムの早期破綻」が想定された。しかし、リボソームRNAのサイズの分布には年齢による明確な違いは見い出せなかった。一方、リボソームで利用されるジストロフィンmRNAの量を決定するnonsense mediated RNA decayの年齢差あるいは、核タンパクの寿命ならびに挙動が「タンパク合成システムの早期破綻」に結びついている可能性も示唆された。

Research Products

• [Journal Article] In vitro splicing analysis reveals that availability of a cryptic splice site is not a determinant for alternative splicing patterns caused by +1G>A mutations in introns of the dystrophin gene. (2008)
  • Author(s): Habara, Y.,Takeshima, Y., Awano, H., Okizuka, Y., Zhang, Z., Saiki, K., Yagi, M., Matsuo, M.
  • Journal Title: J Med Genet. in press. Pages: 0-0
  • Peer Reviewed
• [Journal Article] Wide ranges of serum myostatin concentrations in Duchenne muscular dystrophy patients. (2008)
  • Author(s): Awano, H., Takeshima, Y., Okizuka, Y., Saiki, K., Yagi, M., Matsuo, M.
  • Journal Title: Clin Chim Acta. 391 Pages: 115-117
  • Peer Reviewed
• [Journal Article] Dystrophin nonsense mutations can generate alternative rescue transcrips in lymphocytes. (2008)
  • Author(s): Nisiyama, A., Takeshima, Y., Zhang, Z., Habara, Y., Tran, TH., Yagi, M., Matsuo, M.
  • Journal Title: Ann Hum Genet. 72 Pages: 717-724
  • Peer Reviewed
• [Journal Article] High incidence of electrocardiogram abnormalities in young patients with duchenne muscular dystrophy. (2008)
  • Author(s): Takami, Y., Takeshima, Y., Awano, H., Okizuka, Y., Yagi, M. and Masuo, M.
  • Journal Title: Pediatr. Neurol. 39 Pages: 399-403
  • Peer Reviewed
• [Journal Article] A 2-bp deletion in exon 74 of the dystrophin gene does not clearly induce muscle weakness. (2008)
  • Author(s): Kimura, S. Ito, K. Ueno, H. Ikezawa, M. Takeshima,Y. Yoshioka, K.Ozasa, S. Nakamuara, K. Nomura, K. Matsukura, M. Mitsui, K. Matsuo, M. Miike, T.
  • Journal Title: Brain & Development. 18 Pages: 672-677
  • NAID: 10025578962
  • Peer Reviewed
• [Journal Article] Tandem duplications of two separate fragments of the dystrophin gene in a patient with Duchenne muscular dystrophy. (2008)
  • Author(s): Zhang,Z. Takeshima,Y. Awano,H. Nishiyama,A. Okizuka,Y. Yagi,M. Matsuo,M.
  • Journal Title: J Hum Genet. 53 Pages: 215-219
  • NAID: 10021248166
  • Peer Reviewed
• [Journal Article] A Strong Exonic Splicing Enhancer in Dystrophin Exon 19 achieve proper splicing without an upstream polypyrimidine tract. (2008)
  • Author(s): Habara,Y.Doshita,M.Hirozawa,S. Yokono,Y.Yagi,M.Takeshima,Y. Matsuo,M.
  • Journal Title: J Biochem.143 Pages: 303-310
  • NAID: 10024908594
  • Peer Reviewed
• [Journal Article] A Strong Exonic Splicing Enhancer in Dystrophin Exon 19 achieve proper splicing without an upstream polypyrimidine tract (2008)
  • Author(s): Habara, Y., Matsuo, M., et al
  • Journal Title: J Biochem. 143 Pages: 303-310
  • NAID: 10024908594
  • Peer Reviewed
• [Journal Article] In vitro splicing analysis reveals that availability of a cryptic splice site is not a determinant for alternative splicing patterns caused by+1G>Amutations in introns of the dystrophin gene. (2008)
  • Author(s): Habara, Y., Matsuo, M., et al
  • Journal Title: J Med Genet. (Web)
  • Peer Reviewed
• [Journal Article] In vitro and silico analysis reveals an efficient algorithm to predict the splicing consequences of mutations at the 5' splice sites. (2007)
  • Author(s): Sahashi K, Masuda A, Matsuure T, Shinmi J, Zhang Z, Takeshima Y, Matsuo M, Sobue G, Ohno K.
  • Journal Title: Nucleic Acids Res. Pages: 1-9
  • Peer Reviewed
• [Journal Article] Two novel missense mutations in the myostation gene identified in Japanese patients with Duchenne muscular dystrophy. (2007)
  • Author(s): Nishiyama A, Takeshima Y, Saiki K, Narukage A, Ouazato Y, Yagi M, Matsuo M.
  • Journal Title: BMC Medical Genetics. Pages: 624-630
  • Peer Reviewed
• [Journal Article] A nonsense mutation-created intraexonic splice site is active in the lymphocytes, but not in the skeletal muscle of a DMD patient. (2007)
  • Author(s): Tran VK. Takeshima Y, Zhang Z, Habara Y, Haginoya K, Nishiyama A, Yagi M, Matsuo M.
  • Journal Title: Hum Genet. 120 Pages: 737-742
  • Peer Reviewed
• [Journal Article] Multi-exon skipping leading to an artificial DMD protein lacking amino acids from exons 45 through 55 could rescue up to 63% of patients with Duchenne Muscular Dystrophy. (2007)
  • Author(s): Beroud C, Giraud TS, Matsuo M, Hamroun D., Humbertclaude V, Monnier N, Moizard MP, Voelckel MA, Calemard LM, Boisseau P, Blayau M, Philippe C, Cossee M, Pages M, Rivier F, Danos O, Garcia L, Claustres M.
  • Journal Title: Hum Mutat. 28 Pages: 196-202
  • Peer Reviewed
• [Presentation] Mutation spectrum of the dystrophin gene in 433 Japanese dystrophinopathy cases. (2008)
  • Author(s): Takeshima, Y. Yagi, M. Okizuka, Y. Awano, H. Zang, Z. Saiki, K. Matsuo, M.
  • Organizer: The American Society of Human Genetics 58th Annual Meeting.
  • Year and Date: 2008-11-14
• [Presentation] A novel retrotransposon that was recently inserted into exon 67 of the dystrophin gene. (2007)
  • Author(s): Awano,H. Yagi,M. Okizuka,Y. Zhang,Z. Takeshima,Y. Matsuo,M.
  • Organizer: 57th The American Society of Human Genetics.
  • Year and Date: 2007-10-26
• [Presentation] A complex insertion event produced a chimeric dystrophin-IL1RAPL1 transcript in the dystrophin gene. (2007)
  • Author(s): Zhang,Z. Takeshima,Y. Yagi,M. Nishiyama,A. Okizuka,Y. Awano,H. Matsuo,M.
  • Organizer: 57th The American Society of Human Genetics.
  • Year and Date: 2007-10-26
• [Presentation] Chronological changes of serum creatine kinase(CK)levels in molecularly confirmed Duchenne muscular dystrophy cases and examination of the cases with deviated CK levels. (2007)
  • Author(s): Okizuka,Y. Takeshima,Y. Yagi,M. Oyazato,Y. Awano,H. Zhang,Z. Matsuo,M.
  • Organizer: 57th The American Society of Human Genetics.
  • Year and Date: 2007-10-26
• [Presentation] The Xq28 inversion breakpoint interrupted a novel noncoding gene in a patient with Duchenne muscular dystrophy with severe mental retardation. (2007)
  • Author(s): Yagi,M. Tran Thi,H.T. Zhang,Z. Nishiyama,A. Oyazato,Y. Okinaga,T. Takeshima,Y. Matsuo,M.
  • Organizer: 57th The American Society of Human Genetics.
  • Year and Date: 2007-10-24