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Adenovirus-mediated expression of Myogenic Differentiation Factor 1 (MyoD) in equine and human dermal fibroblasts enables their conversion to caffeine-sensitive myotubes

Fernandez-Fuente, M; Martin-Duque, P; Vassaux, G; Brown, S C; Muntoni, F; Terracciano, C M; Piercy, R J

Authors

M Fernandez-Fuente

P Martin-Duque

G Vassaux

S C Brown

F Muntoni

C M Terracciano

R J Piercy



Abstract

Several human and animal myopathies, such as malignant hyperthermia (MH), central core disease and equine recurrent exertional rhabdomyolysis (RER) are confirmed or thought to be associated with dysfunction of skeletal muscle calcium regulation. For some patients in whom the genetic cause is unknown, or when mutational analysis reveals genetic variants with unclear pathogenicity, defects are further studied through use of muscle histopathology and in vitro contraction tests, the latter in particular, when assessing responses to ryanodine receptor agonists, such as caffeine. However, since muscle biopsy is not always suitable, researchers have used cultured cells to model these diseases, by examining calcium regulation in myotubes derived from skin, following forced expression of muscle-specific transcription factors. Here we describe a novel adenoviral vector that we used to express equine MyoD in dermal fibroblasts. In permissive conditions, transduced equine and human fibroblasts differentiated into multinucleated myotubes. We demonstrate that these cells have a functional excitation-calcium release mechanism and, similarly to primary muscle-derived myotubes, respond in a dose-dependent manner to increasing concentrations of caffeine. MyoD-induced conversion of equine skin-derived fibroblasts offers an attractive method for evaluating calcium homeostasis defects in vitro without the need for invasive muscle biopsy.

Citation

Fernandez-Fuente, M., Martin-Duque, P., Vassaux, G., Brown, S. C., Muntoni, F., Terracciano, C. M., & Piercy, R. J. (2014). Adenovirus-mediated expression of Myogenic Differentiation Factor 1 (MyoD) in equine and human dermal fibroblasts enables their conversion to caffeine-sensitive myotubes. Neuromuscular Disorders, 24(3), 250-258. https://doi.org/10.1016/j.nmd.2013.11.009

Journal Article Type Article
Acceptance Date Nov 18, 2013
Publication Date Mar 1, 2014
Deposit Date Nov 11, 2014
Publicly Available Date Mar 28, 2024
Journal Neuromuscular Disorders
Print ISSN 0960-8966
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 24
Issue 3
Pages 250-258
DOI https://doi.org/10.1016/j.nmd.2013.11.009
Public URL https://rvc-repository.worktribe.com/output/1405897
Additional Information Corporate Creators : Commissariat Energie Atom, Francisco Vitoria, Spain, Harefield Hospital, UCL