Study on dystrophin isoform expressed in heart

• Project/Area Number: 09470182
• 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, Scledicine, Professor, 医学部, 教授 (10157266)
• Co-Investigator(Kenkyū-buntansha): TAKESHIMA Yasuhiro Kobe University, Hospital, Assistant, 医学部・附属病院, 助手 (40281141)
• Project Period (FY): 1997 – 1999
• Project Status: Completed (Fiscal Year 1999)
• Budget Amount: ¥9,000,000 (Direct Cost: ¥9,000,000); Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000); Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000); Fiscal Year 1997: ¥3,500,000 (Direct Cost: ¥3,500,000)
• Keywords: dystrophin / isoform / exon intron / dilated cardiomyopathy / 分子種 / クローニング / 心筋 / アイソフォーム

Research Abstract

The dystrophin gene is the largest gene in human and consists of 79 exons. From this gene many isoforms are produced by using the mechanism of alternative promoters and alternative splicing. In this study new isoform of dystrophin was tried to be identified by reverse-transcription PCR technique. And we succeeded to clone new exon sequence that is located within intron 2. Currently the physiological role of new exon is under the investigation.
We also tried to identify mutation in the promoter/first exon region of the dystrophin gene in dilated cardiomyopathy patients. However, no one had mutation in this region. This showed that mutation in the promoter/first exon region is not responsible for Japanese dilated cardiomyophaty.

Research Products

• [Publications] Shiga, N., Takeshima, Y., Sakamoto, H., Inoue, K., Yokota, Y., Yokoyama, M., and Matsuo, M.: "Disruption of the splicing enhancer sequence within exon 27 of the dystrophin gene by a nonsense mutation induces partial skipping of the exon and is responsible for Becker muscular dystrophy"J. Clin. Invest.. 100. 2204-2210 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Surono, A., Takeshima, Y., Wibawa, T., Pramono, ZA and Matsuo, M.: "Six novel transcripts that remove a huge intron ranging from 250 to 800 kb are produced by alternative splicing of the 5' region of the dystrophin gene in human skeletal muscle"Biochem. Biophys. Res. Commun.. 239. 895-899 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shiga, N., Matsuo, M., Yokoyama, M and Yokota, Y.: "Study on mutations affecting the muscle promoter/first exon of the dystrophin gene in 92 Japanese dilated cardiomyopathy patients"Am. J. Med. Genet.. 79. 226-227 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Chen, D.H., Takeshima, Y., Y. Ishikawa, Y. Minami, R and Matsuo, M.: "A novel deletion of the dystrophin S-promoter region consegregating with mental retardation"Neurology. 52. 638-640 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Surono, A., Takeshima, Y., Wibawa, T., Pramono, ZA and Matsuo, M.: "Circular dystrophin RNAs consisting of exons that were skipped by alternative splicing"Hum. Mol. Genet.. 8. 493-500 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Dwi Pramono, Z.A., Takeshima, Y., Surono, A., Ishida, T., and Matsuo, M.: "A novel cryptic exon in intron 2 of the human dystrophin gene evolved from an intron by acquiring consensus sequences for splicing at different stages of anthropoid evolution"Biochem. Biophys. Res. Commun.. 267. 321-328 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shiga,N, Takeshima,Y, Sakamoto,H, Inoue,K, Yokota,Y, Yokoyama,M and Matsuo,M.: "Disruption of the splicing enhancer sequence within exon 27 of the dystrophin gene by a nonsense mutation induces partial skipping of the exon and is responsible for Becker muscular dystrophy"J Clin Invest. 100. 2204-2210 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ishigaki,C, Patria,SY, Nishio,H, Yoshioka,A and Matsuo,M.: "Early cardiac failure in a child with Becker muscular dystrophy is due to an abnormally low amount of dystrophin transcript lacking exon 13"Acta Paediartr Jpn. 39. 685-689 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Inoue,M, Honda,S, Nishio,H, Matsuo,M, Nakamura,H and Yamamoto,M.: "Genotype and electroretinal heterogeneity in Duchenne muscular dystrophy"Exp Eye Res. 65. 861-864 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Surono,A, Takeshima,Y, Wibawa,T, Pramono,ZA and Matsuo,M.: "Six novel transcripts that remove a huge intron ranging from 250 to 800 kb are produced b alternative splicing of the 5' region of the dystrophin gene in human skeletal muscle"Biochem Biophys Res Commun. 239. 895-899 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tachi,N, Ohya,K, Chiba,S, Matsuo,M Patria,SY and Matsumura,K.: "Deficiency of syntrophin, dystroglycan, and merosin in a female infant with a congenital muscular dystrophy phenotype lacking cysteine-rich and C-terminal domains of dystrophin"Neurology. 49. 579-583 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shiga,N, Matsuo,M, Yokoyama,M and Yokota,Y.: "Study on mutations affecting the muscle promoter/first exon of the dystrophin gene in 92 Japanese dilated cardiomyopathy patients"Am J Med Genet. 79. 226-227 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Chen,DH, Takeshima,Y, Ishikawa,Y, Minami,R and Matsuo,M.: "A novel deletion of the dystrophin S-promoter region cosegregating with mental retardation"Neurology. 52. 638-640 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Surono,A, Takeshima,Y, Wibawa,T, Ikezawa,M, Nonaka,I and Matsuo,M.: "Circular dystrophin RNAs consisting of exons that were skipped by alternative splicing"Hum Mol Genet. 8. 493-500 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Patria,SY, Takeshima,Y, Suminaga,R, Nakamura,H, Iwasaki,R, Minagawa,T and Matsuo,M.: "A simple explanation for a case of incompatibility with the reading frame theory in Duchenne muscular dystrophy : failure to detect an aberrant restriction fragment in Southern blot analysis"Brain Dev. 21. 386-389 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Dwi Pramono,ZA, Takeshima,Y, Surono,A, Ishida,T and Matsuo,M.: "A novel cryptic exon in intron 2 of the human dystrophin gene evolved from an intron by acquiring consensus sequences for splicing at different stages of anthropoid evolution"Biochem Biophys Res Commun. 267. 321-328 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wibawa,T, Takeshima,Y, Mitsuyoshi,IW,H., Surono,A, Nakamura,H and Matsuo,M.: "Complete skipping of exon 66 due to novel mutations of the dystrophin gene was identified in two Japanese families of DMD with severe mental retardation"Brain Dev. (in press). (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Chen,DH,Takeshima,Y,Ishikawa,Y,Minami,R and Matsuo,M.: "A novel deletion of the dystrophin S-promoter region cosegregating with mental retardation"Neurology. 52. 638-640 (1999)
• [Publications] Surono,A,Takeshima,Y,Wibawa,T,Ikezawa,M,Nonaka,I and Matsuo,M.: "Circular dystrophin RNAs consisting of exons that were skipped by alternative splicing"Hum Mol Genet. 8. 493-500 (1999)
• [Publications] Patria,SY,Takeshima,Y,Suminaga,R,Nakamura,H,Iwasaki,R,Minagawa,T and Matsuo,M.: "A simple explanation for a case of incompatibility with the reading frame theory in Duchenne muscular dystrophy: failure to detect an aberrant restriction fragment in Southern blot analysis"Brain Dev. 21. 386-389 (1999)
• [Publications] Dwi Pramono,ZA,Takeshima,Y,Surono,A,Ishida,T and Matsuo,M.: "A novel cryptic exon in intron 2 of the human dystrophin gene evolved from an intron by acquiring consensus sequences for splicing at different stages of anthropoid evolution"Biochem Biophys Res Commun. 267. 321-328 (2000)
• [Publications] Wibawa,T,Takeshima,Y,Mitsuyoshi,H,Surono,A,Nakamura,H and Matsuo,M.: "Complete skipping of exon 66 due to novel mutations of the dystrophin gene was identified in two Japanese families of DMD with severe mental retardation"Brain Dev. (in press). (2000)
• [Publications] Shiga,N,Matsuo,M.Yokoyama,M,Yokota,Y.: "Study on mutations affecting the muscle promoter/first exon of the dystrophin gene in 92 Japanese dilated cardionmyopathy patients." Am J Med Genet.79. 226-227 (1998)
• [Publications] Surono,A,Takeshima,Y,Wibawa,T,Ikezawa,M,Nonaka,I,Matsuo,M.: "Circular dystrophin RNAs consisting of exons that were skipped by alternatve splicing." Hum Mol Genet.8. 493-500 (1999)
• [Publications] Chen,D,Takeshima,Y,Ishikawa,Y,Ishikawa,Y,Minami,R,Matsuo,M.: "A novel deletion of the dystrophin S-promoter region co-segregting with mental retardation." Neurology. (in press). (1999)
• [Publications] Shiga,N., Y.Takeshima, H.Sakamoto,K. et al.: "Disruption of the splicing enhancer sequence within exon 27 of the dystrophin gene by a nonsense mutation induses partial skipping of the exon and is responsible for Becker muscular dystrophy." J. Clin. Invest.100. 2204-2210 (1997)
• [Publications] Surono,A., Y.Takeshima, T.Wibawa, Z.A.D. et al.: "Six novel transcripts that remove a huge intron ranging from 250 kb to 800kb are produced by alternative splicing of the 5' region of the dystrophin gene in human skeletal muscle." Biochem. Biophys. Res. Commun.239. 895-899 (1997)
• [Publications] Ishigaki,C., S. Y. Patria, H. Nishio, A. et al.: "Early cardiac failure in a child with Beckr muscular dystrophy is due to an abnormally low amount of dystrophin transcript lacking exon 13." Acta Paediatr. Jap.39. 685-689 (1997)
• [Publications] Tachi,N., K.Ohta, S.Chiba, M.Matsuo et al.: "Deficiency of syntrophin, dystroglycan, and merosin in a female infant with a congenital muscular dystrophy phenotype lacking cysteine-rich and C-terminal domains of dystrophin." Neurology. 49. 579-583 (1997)