Revertant Fibers in the mdx Murine Model of Duchenne Muscular Dystrophy: An Age- and Muscle-Related reappraisal

D. Fraidenraich; S.R. Pigozzo; L. Da Re; C. Romualdi; P.G. Mazzara; E. Galletta; S. Fletcher; S.D. Wilton; L. Vitiello

doi:10.1371/journal.pone.0072147

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Revertant Fibers in the mdx Murine Model of Duchenne Muscular Dystrophy: An Age- and Muscle-Related reappraisal

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Revertant Fibers in the mdx Murine Model of Duchenne Muscular Dystrophy: An Age- and Muscle-Related reappraisal

D. Fraidenraich, S.R. Pigozzo, L. Da Re, C. Romualdi, P.G. Mazzara, E. Galletta, S. Fletcher, S.D. Wilton and L. Vitiello

PLoS ONE, Vol.8(8), e72147

2013

DOI: https://doi.org/10.1371/journal.pone.0072147

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Abstract

Muscles in Duchenne dystrophy patients are characterized by the absence of dystrophin, yet transverse sections show a small percentage of fibers (termed “revertant fibers”) positive for dystrophin expression. This phenomenon, whose biological bases have not been fully elucidated, is present also in the murine and canine models of DMD and can confound the evaluation of therapeutic approaches. We analyzed 11 different muscles in a cohort of 40 mdx mice, the most commonly model used in pre-clinical studies, belonging to four age groups; such number of animals allowed us to perform solid ANOVA statistical analysis. We assessed the average number of dystrophin-positive fibers, both absolute and normalized for muscle size, and the correlation between their formation and the ageing process. Our results indicate that various muscles develop different numbers of revertant fibers, with different time trends; besides, they suggest that the biological mechanism(s) behind dystrophin re-expression might not be limited to the early development phases but could actually continue during adulthood. Importantly, such finding was seen also in cardiac muscle, a fact that does not fit into the current hypothesis of the clonal origin of “revertant” myonuclei from satellite cells. This work represents the largest, statistically significant analysis of revertant fibers in mdx mice so far, which can now be used as a reference point for improving the evaluation of therapeutic approaches for DMD. At the same time, it provides new clues about the formation of revertant fibers/cardiomyocytes in dystrophic skeletal and cardiac muscle.

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Title: Revertant Fibers in the mdx Murine Model of Duchenne Muscular Dystrophy: An Age- and Muscle-Related reappraisal
Authors/Creators: D. Fraidenraich (Author/Creator)
S.R. Pigozzo (Author/Creator) - Queen Elizabeth II Medical Centre
L. Da Re (Author/Creator) - University of Padua
C. Romualdi (Author/Creator) - University of Padua
P.G. Mazzara (Author/Creator) - University of Padua
E. Galletta (Author/Creator) - University of Padua
S. Fletcher (Author/Creator) - Queen Elizabeth II Medical Centre
S.D. Wilton (Author/Creator) - Queen Elizabeth II Medical Centre
L. Vitiello (Author/Creator) - University of Padua
Publication Details: PLoS ONE, Vol.8(8), e72147
Publisher: Public Library of Science
Identifiers: 991005540197007891
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.255 Musculoskeletal Disorders; 1.255.628 Duchenne Muscular Dystrophy
Web Of Science research areas: Clinical Neurology
ESI research areas: Neuroscience & Behavior