Functional analysis of muscle-specific protein, ARPP, expressed in the atrophic skeletal muscles

最近，我们发现了一种新的人类蛋白质，具有PEST和富含脯氨酸区域的锚定重复蛋白（ARPP）。ARPP的结构特征是在其中心部分存在四个锚定重复结构域。ARPP的氨基酸序列与心脏限制性锚定重复蛋白（CARP; 52%）高度同源。我们观察到ARPP在骨骼肌和心脏中的高表达水平。ARPP选择性表达于骨骼肌的1型肌纤维，因此，ARPP阳性肌纤维排列成棋盘状图案。本研究通过建立ARPP基因敲除（KO）小鼠模型，分析ARPP在体内的功能。我们的研究结果如下：1）与正常小鼠相比，ARPP基因敲除小鼠耐力训练后运动能力下降2）失神经支配10周可诱导骨骼肌中ARPP的表达; 3）尾部悬吊诱导废用性萎缩骨骼肌中ARPP的表达显著下调。ARPP基因敲除小鼠在神经系统和骨骼肌特异性表达的基因中表现出不同的表达模式。ARPP基因敲除小鼠在注射心脏毒素后表现出较正常小鼠严重的肌肉损伤和坏死组织的清除延迟，提示ARPP基因敲除小鼠可能与其诱导表达的几种蛋白质有关，这些蛋白质在肌肉性能、肌肉损伤和肌肉再生中起着重要的作用。

Recently, we identified a novel human protein, ankyrin-repeated protein with PEST and praline-rich region (ARPP). ARPP is characterized structurally by the presence of four ankyrin-repeated domains in its central portion. The amino acid sequence of ARPP is highly homologous with that of cardiac restricted ankyrin-repeated protein (CARP; 52%). We observed high expression levels of ARPP in skeletal muscle and the heart. ARPP was selectively expressed in type 1 myofibers of skeletal muscle and, therefore, ARPP-positive myofibers were arranged in a checkerboard-like pattern. In this study, we analyzed the function of ARPP in vivo by generating ARPP knock-out (KO) mouse. Our findings are as follows;1) Compared with normal mouse, ARPP KO mouse showed decreased exercise capacity for endurance training2) ARPP expression in the skeletal muscle was found to be induced by denervation for 10 weeks.3) ARPP expression in the disuse atrophic skeletal muscle induced by tail-suspension was significantly down-regulated.4) ARPP KO mouse showed distinct expression pattern of some genes expressed specifically in the nervous system as well as skeletal muscle specific genes.5) ARPP KO mouse showed much more severe muscle injury induced by injection of cardiotoxin and delayed clearance of necrotic tissue compared with normal mouseThese findings suggest that ARPP might be concerned with the induced expression of the several proteins acting as the procetive effects in the muscle performance, muscle injury and muscle regeneration.