Study on neuron-specific aberrant splicings in myotonic dystrophies

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659455
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Okayama University
• Principal Investigator: MATSUURA Tohru 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (90402560)
• Co-Investigator(Kenkyū-buntansha): IKEDA Yoshio 岡山大学, 岡山大学病院, 講師 (00282400)
• Project Period (FY): 2011 – 2012
• Keywords: 筋強直性ジストロフィー / 優性遺伝性非翻訳リピート病 / スプライシング / RNA

Research Abstract

Myotonic dystrophy type 1 (DM1) is an RNA gain-of-function disorder, in which abnormally expanded CTG repeats of DMPK sequestrate a splicing trans-factor MBNL1 and upregulate another splicing trans-factor CUGBP1. To identify a diverse array of aberrantly spliced genes, we performed the exon array analysis of DM1 muscles and brains. We analyzed by RT-PCR and found that 12 exons were aberrantly spliced. Furthermore, we studied the molecular mechanism underlying these aberrant splicings and their pathogenicity.

Research Products

• [Journal Article] Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour (2013)
  • Author(s): Hernandez-Hernandez O, Guiraud-Dogan C, Sicot G, Huguet A, Luilier S, Steidl E, Saenger S, Marciniak E, Obriot H, Chevarin C, Nicole A, Revillod L, Charizanis K, Lee KY, Suzuki Y, Kimura T, Matsuura T, Cisneros B, Swanson MS, Trovero F, Buisson B, Bizot JR, Hamon M, Humez S, Bassez G, Metzger F, Buee L, Munnich A, Sergeant N, Gourdon G, Gomes-Pereira M.
  • Journal Title: Brain Volume: 136 (Pt 3) Pages: 957-70
  • Peer Reviewed
• [Journal Article] The unstable CCTG repeat responsible for myotonic dystrophy type 2 originates from an AluSx element insertion into an early primate genome. (2012)
  • Author(s): Kurosaki T, Ueda S, Ishida T, Abe K, Ohno K, Matsuura T.
  • Journal Title: PLoS ONE Volume: 7 Pages: e38379
  • Peer Reviewed
• [Journal Article] Myotonic dystrophy type 2 (DM2) is rare in the Japanese population. (2012)
  • Author(s): Matsuura T, Minami N, Arahata H, Ohno K, Abe K, Hayashi YK, Nishino I.
  • Journal Title: J Hum Genet Volume: 57 Pages: 219-20
  • Peer Reviewed
• [Journal Article] Four parameters increase the sensitivity and specificity of the exon array analysis and disclose twenty-five novel aberrantly spliced exons in myotonic dystrophy. (2012)
  • Author(s): #Yamashita Y, #Matsuura T(#equally contributed), Shinmi J, Amakusa Y, Masuda A, Ito M, Kinoshita M, Furuya H, Abe K, Ibi T, Sahashi K, Ohno K.
  • Journal Title: J Hum Genet Volume: 57 Pages: 368-74
  • Peer Reviewed
• [Journal Article] Effect of mitochondrial transcription factor A overexpression on motor neurons in amyotrophic lateral sclerosis model mice (2012)
  • Author(s): Morimoto N, Miyazaki K, Sato K, Kurata T, Ikeda Y, Matsuura T, Dongchon K, Ide T, Abe K.
  • Journal Title: J Neurosci Res Volume: 90 Pages: 1200-8
  • Peer Reviewed
• [Journal Article] Comparisons of acoustic function in SCA31 and other forms of ataxias. (2011)
  • Author(s): Ikeda Y, Nagai M, Kurata T, Yamashita T, Ohta Y, Nagotani S, Deguchi K, Takehisa Y, S h ir o Y, Matsuura T, Abe K.
  • Journal Title: Neurol Res Volume: 33 Pages: 427-32
  • Peer Reviewed
• [Journal Article] Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes a type of spinocerebellar ataxia (SCA36) accompanied by motor neuron involvement. (2011)
  • Author(s): #Kobayashi H, #Abe K,#Matsuura T(#equally contributed),Ikeda Y,Hitomi T, Akechi Y, Habu T, Yang LW, Okuda H, Koizumi A.
  • Journal Title: Am J Hum Genet Volume: 89 Pages: 121-30
  • Peer Reviewed
• [Journal Article] Hyperuricemia cosegregating with osteogenesis imperfecta is associated with a mutation in GPATCH8 (2011)
  • Author(s): Kaneko H, Kitoh H, Matsuura TMasuda A, Ito M, Mottes M, Rauch F, Ishiguro N, Ohno K.
  • Journal Title: Hum Genet Volume: 130 Pages: 671-83
  • Peer Reviewed
• [Presentation] RNA-mediated disease mechanism of spinocerebellar ataxia type 10. (2012)
  • Author(s): Matsuura T, Kurosaki T, Muramatsu S, Shimazaki K, Ohno K, and Abe K.
  • Organizer: 7th International Conference on Unstable Microsatellites and Human Disease.
  • Place of Presentation: Strasbourg(France)
  • Year and Date: 20120609-14
• [Presentation] 新しいALS/SCA cross road mutation AsidanのRNA病態メカニズム解析 (2012)
  • Author(s): 松浦 徹、明地雄司、池田佳生、森本展年、宮崎一徳、阿部康二 小林果、小泉昭夫
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 20120522-25
• [Remarks]
  • URL: http://www.okayama-u.ac.jp/user/med/shinkeinaika/index.htm
• [Remarks]
  • URL: http://square.umin.ac.jp/channel/sub3.html