Journal article
Common pathological mechanisms in mouse models for muscular dystrophies
The FASEB journal, Vol.20(1), pp.127-129
01/2006
DOI: 10.1096/fj.05-4678fje
PMID: 16306063
Abstract
Duchenne/Becker and limb‐girdle muscular dystrophies share clinical symptoms like muscle weakness and wasting but differ in clinical presentation and severity. To get a closer view on the differentiating molecular events responsible for the muscular dystrophies, we have carried out a comparative gene expression profiling of hindlimb muscles of the following mouse models: dystrophin‐deficient (mdx, mdx3cv), sarcoglycan‐deficient (Sgca null, Sgcb null, Sgcg null, Sgcd null), dysferlin‐deficient (Dysf null, SJLDysf), sarcospan‐deficient (Sspn null), and wild‐type (C57Bl/6, C57Bl/10) mice. The expression profiles clearly discriminated between severely affected (dystrophinopathies and sarcoglycanopathies) and mildly or nonaffected models (dysferlinopathies, sarcospan‐deficiency, wild‐type). Dystrophin‐deficient and sarcoglycandeficient profiles were remarkably similar, sharing inflammatory and structural remodeling processes. These processes were also ongoing in dysferlin‐deficient animals, albeit at lower levels, in agreement with the later age of onset of this muscular dystrophy. The inflammatory proteins Spp1 and S100a9 were up‐regulated in all models, including sarcospan‐deficient mice, which points, for the first time, at a subtle phenotype for Sspn null mice. In conclusion, we identified biomarker genes for which expression correlates with the severity of the disease, which can be used for monitoring disease progression. This comparative study is an integrating step toward the development of an expression profiling‐based diagnostic approach for muscular dystrophies in humans.
Details
- Title: Subtitle
- Common pathological mechanisms in mouse models for muscular dystrophies
- Creators
- R Turk - Howard Hughes Medical InstituteE Sterrenburg - Center for Human and Clinical GeneticsC. G. C Wees - Center for Human and Clinical GeneticsE. J Meijer - Center for Human and Clinical GeneticsR. X Menezes - Center for Human and Clinical GeneticsS Groh - Howard Hughes Medical InstituteK. P Campbell - Howard Hughes Medical InstituteS Noguchi - National Institute of NeuroscienceG. J. B Ommen - Center for Human and Clinical GeneticsJ. T Dunnen - Center for Human and Clinical GeneticsP. A. C. 't Hoen - Center for Human and Clinical Genetics
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.20(1), pp.127-129
- DOI
- 10.1096/fj.05-4678fje
- PMID
- 16306063
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 29
- Grant note
- Center for Biomedical Genetics Nederlandse Stichting voor Wetenschappelijk Onderzoek Centre for Medical Systems Biology Netherlands Genomics Initiative/Netherlands Organization for Scientific Research
- Language
- English
- Date published
- 01/2006
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020777202771
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