decreased proliferation kinetics of mouse myoblasts overexpressing frg1降低小鼠成肌细胞的增殖动力学overexpressing frg1.pdf

Decreased Proliferation Kinetics of Mouse Myoblasts Overexpressing FRG1 1 1¤a 1 2 1¤b 2 Steven C. Chen , Ellie Frett , Joseph Marx , Darko Bosnakovski , Xylena Reed , Michael Kyba , Brian K. Kennedy1,3* 1 Department of Biochemistry, University of Washington, Seattle, Washington, United States of America, 2 Lillehei Heart Institute and Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, United States of America, 3 Buck Institute for Age Research, Novato, California, United States of America Abstract 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 pla