Decreased Proliferation Kinetics of Mouse Myoblasts Overexpressing FRG1

Brigham and Women's Hospital, Harvard Medical School, United States of America
PLoS ONE (Impact Factor: 3.23). 05/2011; 6(5):e19780. DOI: 10.1371/journal.pone.0019780
Source: PubMed


Although recent publications have linked the molecular events driving facioscapulohumeral muscular dystrophy (FSHD) to expression of the double homeobox transcription factor DUX4, overexpression of FRG1 has been proposed as one alternative causal agent as mice overexpressing FRG1 present with muscular dystrophy. Here, we characterize proliferative defects in two independent myoblast lines overexpressing FRG1. Myoblasts isolated from thigh muscle of FRG1 transgenic mice, an affected dystrophic muscle, exhibit delayed proliferation as measured by decreased clone size, whereas myoblasts isolated from the unaffected diaphragm muscle proliferated normally. To confirm the observation that overexpression of FRG1 could impair myoblast proliferation, we examined C2C12 myoblasts with inducible overexpression of FRG1, finding increased doubling time and G1-phase cells in mass culture after induction of FRG1 and decreased levels of pRb phosphorylation. We propose that depressed myoblast proliferation may contribute to the pathology of mice overexpressing FRG1 and may play a part in FSHD.

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Available from: Brian K Kennedy, Sep 15, 2014
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    • "imb in vitro . Using the Nestin - GFP mouse model ( Day et al . , 2007 ) to identify self - renewal of myoblasts , Stuelsatz et al . ( 2014 ) found higher percentages of GFP + cells in diaphragm verses limb muscle cultures . In vitro clonal expansion assays revealed that diaphragmatic myoblasts proliferated similarly to those of hindlimb muscles ( Chen et al . , 2011 ; Stuelsatz et al . , 2012 ) , but myogenic differentiation of diaphragm cultures consistently reached maximum fusion indexes earlier than limb cultures ( Stuelsatz et al . , 2014 ) . However , other studies demonstrated that diaphragmatic satellite cells undergo increased proliferation and decreased differentiation in vitro when compar"
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