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    Comparative proteomic profiling of soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscles from the mdx mouse model of Duchenne muscular dystrophy


    Carberry, Steven and Brinkmeier, Heinrich and Zhang, Yaxin and Winkler, Claudia K. and Ohlendieck, Kay (2013) Comparative proteomic profiling of soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscles from the mdx mouse model of Duchenne muscular dystrophy. International Journal of Molecular Medicine, 32 (374). pp. 544-556. ISSN 1107-3756

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    Abstract

    Duchenne muscular dystrophy is due to genetic abnormalities in the dystrophin gene and represents one of the most frequent genetic childhood diseases. In the X-linked muscular dystrophy (mdx) mouse model of dystrophinopathy, different subtypes of skeletal muscles are affected to a varying degree albeit the same single base substitution within exon 23 of the dystrophin gene. Thus, to determine potential muscle subtype-specific differences in secondary alterations due to a deficiency in dystrophin, in this study, we carried out a comparative histological and proteomic survey of mdx muscles. We intentionally included the skeletal muscles that are often used for studying the pathomechanism of muscular dystrophy. Histological examinations revealed a significantly higher degree of central nucleation in the soleus and extensor digitorum longus muscles compared with the flexor digitorum brevis and interosseus muscles. Muscular hypertrophy of 20-25% was likewise only observed in the soleus and extensor digitorum longus muscles from mdx mice, but not in the flexor digitorum brevis and interosseus muscles. For proteomic analysis, muscle protein extracts were separated by fluorescence two-dimensional (2D) gel electrophoresis. Proteins with a significant change in their expression were identified by mass spectrometry. Proteomic profiling established an altered abundance of 24, 17, 19 and 5 protein species in the dystrophin-deficient soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscle, respectively. The key proteomic findings were verified by immunoblot analysis. The identified proteins are involved in the contraction-relaxation cycle, metabolite transport, muscle metabolism and the cellular stress response. Thus, histological and proteomic profiling of muscle subtypes from mdx mice indicated that distinct skeletal muscles are differentially affected by the loss of the membrane cytoskeletal protein, dystrophin. Varying degrees of perturbed protein expression patterns in the muscle subtypes from mdx mice may be due to dissimilar downstream events, including differences in muscle structure or compensatory mechanisms that counteract pathophysiological processes. The interosseus muscle from mdx mice possibly represents a naturally protected phenotype.

    Item Type: Article
    Additional Information: This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited: Carberry, S., Brinkmeier, H., Zhang, Y., Winkler, C. K., Ohlendieck, K."Comparative proteomic profiling of soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscles from the mdx mouse model of Duchenne muscular dystrophy". International Journal of Molecular Medicine 32, no. 3 (2013): 544-556. http://dx.doi.org/10.3892/ijmm.2013.1429
    Keywords: dystrophinopathy; muscle dystrophic x-linked; muscular dystrophy; interosseus muscle; flexor digitorum brevis muscle;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 6901
    Identification Number: https://doi.org/10.3892/ijmm.2013.1429
    Depositing User: Prof. Kay Ohlendieck
    Date Deposited: 21 Jan 2016 14:51
    Journal or Publication Title: International Journal of Molecular Medicine
    Publisher: Spandidos Publications
    Refereed: Yes
    Funders: Muscular Dystrophy Ireland, European Commission, Aktion Benni & Co e.V., Hume Scholarship, Health Research Board (HRB), Higher Education Authority (HEA)
    URI:

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