Facioscapulohumeral muscular dystrophy region gene 1 over-expression causes primary defects of myogenic stem cells.

Journal of Cell Science (Impact Factor: 5.43). 03/2013; 126(10). DOI: 10.1242/jcs.121533
Source: PubMed

ABSTRACT

Over-expression of FSHD Region Gene 1 (FRG1) in mice, frogs and worms leads to muscular and vascular abnormalities. Nevertheless, the mechanism that follows FRG1 over-expression and finally leads to muscular defects is currently unknown. Here, we show that the earliest phenotype displayed by FRG1 mice is a postnatal muscle-growth defect. Long before the development of muscular dystrophy, FRG1 mice exhibit also a muscle regeneration impairment. Ex-vivo and in-vivo experiments revealed that FRG1 over-expression causes myogenic stem-cell activation, proliferative, clonogenic and differentiation defects. A comparative gene expression profiling of WT and FRG1 muscles from young pre-dystrophic mice identified differentially expressed genes in several gene categories and networks that could explain the emerging tissue and myogenic stem-cell defects. Overall, our study provides new insights in the pathways regulated by FRG1 and suggests that muscle-stem cells defects could contribute to the pathology of FRG1 mice.

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