Journal article
Long-term administration of antisense oligonucleotides into the paraspinal muscles of mdx mice reduces kyphosis
Journal of Applied Physiology, Vol.105(2), pp.662-668
2008
Abstract
The mdx mouse model of muscular dystrophy has a premature stop codon preventing production of dystrophin. This results in a progressive phenotype causing centronucleation of skeletal muscle fibers, muscle weakness, and fibrosis and kyphosis. Antisense oligonucleotides alter RNA splicing to exclude the nonsense mutation, while still maintaining the open reading frame to produce a shorter, but partially functional dystrophin protein that should ameliorate the extent of pathology. The present study investigated the benefits of chronic treatment of mdx mice by oncemonthly deep intramuscular injections of antisense oligonucleotides into paraspinal muscles. After 8 mo of treatment, mdx mice had reduced development of kyphosis relative to untreated mdx mice, a benefit that was retained until completion of the study at 18 mo of age (16 mo of treatment). This was accompanied by reduced centronucleation in the latissimus dorsi and intercostals muscles and reduced fibrosis in the diaphragm and latissimus dorsi. These benefits were accompanied by a significant increase in dystrophin production. In conclusion, chronic antisense oligonucleotide treatment provides clear and ongoing benefits to paralumbar skeletal muscle, with associated marked reduction in kyphosis.
Details
- Title
- Long-term administration of antisense oligonucleotides into the paraspinal muscles of mdx mice reduces kyphosis
- Authors/Creators
- N. Laws (Author/Creator)R.A. Cornford-Nairn (Author/Creator)N. Irwin (Author/Creator)R. Johnsen (Author/Creator)S. Fletcher (Author/Creator)S.D. Wilton (Author/Creator)A.J. Hoey (Author/Creator)
- Publication Details
- Journal of Applied Physiology, Vol.105(2), pp.662-668
- Publisher
- American Physiological Society
- Identifiers
- 991005541839907891
- Copyright
- © 2008 the American Physiological Society
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.255 Musculoskeletal Disorders
- 1.255.628 Duchenne Muscular Dystrophy
- Web Of Science research areas
- Physiology
- Sport Sciences
- ESI research areas
- Biology & Biochemistry