Decreased Proliferation Kinetics of Mouse Myoblasts Overexpressing FRG1
Decreased Proliferation Kinetics of Mouse Myoblasts Overexpressing FRG1
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DOI：
10.1371/journal.pone.0019780
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发表时间：
2011-05-16
期刊：
影响因子：
3.7
通讯作者：
Kennedy, Brian K.
中科院分区：
文献类型：
--
作者：
Chen, Steven C.;Frett, Ellie;Kennedy, Brian K.
尽管最近的文献已将FSHD的分子事件与双同源盒转录因子DUX4的表达联系在一起，但FRG1的过度表达已被认为是一种替代的病因，因为FRG1过度表达的小鼠出现了肌肉营养不良。在这里，我们描述了两个独立的过表达FRG1的成肌细胞系的增殖性缺陷。从FRG1转基因小鼠的大腿肌肉分离的成肌细胞是一种营养不良的肌肉，通过减少克隆大小来衡量，显示出延迟的增殖，而从未受影响的横隔肌分离的成肌细胞则正常增殖。为了证实过表达FRG1会损害成肌细胞的增殖，我们检测了诱导过表达FRG1的C2C12成肌细胞，发现在诱导FRG1后，大量培养的细胞倍增时间延长，G1期细胞增加，pRb磷酸化水平降低。我们认为，成肌细胞增殖抑制可能是FRG1过表达小鼠的病理机制之一，并可能在FSHD中起一定作用。
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.