Brief Communication

Inhibition of nonsense-mediated mRNA decay rescues the phenotype in Ullrich's disease

  1. Fusako Usuki MD1,*,
  2. Akio Yamashita PhD2,†,
  3. Itsuro Higuchi MD3,
  4. Tetsuo Ohnishi PhD2,‡,
  5. Tadafumi Shiraishi MD3,
  6. Mitsuhiro Osame MD3,
  7. Shigeo Ohno PhD2

Article first published online: 26 APR 2004

DOI: 10.1002/ana.20107

Issue

Annals of Neurology

Annals of Neurology

Volume 55, Issue 5, pages 740–744, May 2004

Additional Information

How to Cite

Usuki, F., Yamashita, A., Higuchi, I., Ohnishi, T., Shiraishi, T., Osame, M. and Ohno, S. (2004), Inhibition of nonsense-mediated mRNA decay rescues the phenotype in Ullrich's disease. Ann Neurol., 55: 740–744. doi: 10.1002/ana.20107

Author Information

  1. 1

    Department of Clinical Medicine, National Institute for Minamata Disease, Hama, Minamata, Japan

  2. 2

    Department of Molecular Biology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan

  3. 3

    Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Science, 8-35-1 Sakuragaoka, Kagoshima, Japan

  1. †

    Department of Biochemistry and Molecular Biology, University of Texas, Houston, TX 77030

  2. ‡

    Laboratory for Molecular Psychiatry, Brain Science Institute, RIKEN, WAKO 351-0198, Japan

*Department of Clinical Medicine, National Institute for Minamata Disease, 4058-18 Hama, Minamata 867-0008, Japan

Publication History

  1. Issue published online: 26 APR 2004
  2. Article first published online: 26 APR 2004
  3. Manuscript Accepted: 4 MAR 2004
  4. Manuscript Revised: 1 MAR 2004
  5. Manuscript Received: 22 DEC 2003

Funded by

  • Ministry of Health Labor and Welfare. Grant Number: 11B-1
  • Ministry of Education, Science, Sports and Culture, Japan
  • The Mitsubishio Foundation
  • Japan Science and Technology Agency

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Abstract

Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance system that eliminates aberrant mRNAs containing premature translation termination codons (PTCs). We evaluated the role of NMD in of Ullrich's disease. The patient has a frameshift mutation with a PTC in the collagen VI α2 gene causing the loss of collagen VI and functional defects in extracellular matrix (ECM). The pharmacological block of NMD caused upregulation of the mutant collagen VI α2 subunit, resulting in collagen VI assembly and partially functional ECM formation. Our results suggest that NMD inhibitors can be used as a therapeutic tool to rescue some human genetic diseases exacerbated by NMD.

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