Time Course Analysis of Skeletal Muscle Pathology of GDE5 Transgenic MouseReportar como inadecuado

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Glycerophosphodiesterase 5 GDE5 selectively hydrolyses glycerophosphocholine to choline and is highly expressed in type II fiber-rich skeletal muscles. We have previously generated that a truncated mutant of GDE5 GDE5dC471 that lacks phosphodiesterase activity and shown that transgenic mice overexpressing GDE5dC471 in skeletal muscles show less skeletal muscle mass than control mice. However, the molecular mechanism and pathophysiological features underlying decreased skeletal muscle mass in GDE5dC471 mice remain unclear. In this study, we characterized the skeletal muscle disorder throughout development and investigated the primary cause of muscle atrophy. While type I fiber-rich soleus muscle mass was not altered in GDE5dC471 mice, type II fiber-rich muscle mass was reduced in 8-week-old GDE5dC471 mice. Type II fiber-rich muscle mass continued to decrease irreversibly in 1-year-old transgenic mice with an increase in apoptotic cell. Adipose tissue weight and blood triglyceride levels in 8-week-old and 1-year-old transgenic mice were higher than those in control mice. This study also demonstrated compensatory mRNA expression of neuromuscular junction NMJ components, including nicotinic acetylcholine receptors α1, γ, and ε subunits and acetylcholinesterase in type II fiber-rich quadriceps muscles in GDE5dC471 mice. However, we did not observe morphological changes in NMJs associated with skeletal muscle atrophy in GDE5dC471 mice. We also found that HSP70 protein levels are significantly increased in the skeletal muscles of 2-week-old GDE5dC471 mice and in mouse myoblastic C2C12 cells overexpressing GDE5dC471. These findings suggest that GDE5dC471 mouse is a novel model of early-onset irreversible type II fiber-rich myopathy associated with cellular stress.

Autor: Takao Hashimoto , Bo Yang , Yuri Okazaki , Ikumi Yoshizawa, Kaori Kajihara, Norihisa Kato, Masanobu Wada, Noriyuki Yanaka

Fuente: http://plos.srce.hr/


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