Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
PLoS One. 2012;7(5):e37702. doi: 10.1371/journal.pone.0037702. Epub 2012 May 25.
Growth arrest-specific gene 7 (Gas7) has previously been shown to be involved in neurite outgrowth in vitro; however, its actual role has yet to be determined. To investigate the physiological function of Gas7 in vivo, here we generated a Gas7-deficient mouse strain with a labile Gas7 mutant protein whose functions are similar to wild-type Gas7.
METHODOLOGY/PRINCIPAL FINDINGS: Our data show that aged Gas7-deficient mice have motor activity defects due to decreases in the number of spinal motor neurons and in muscle strength, of which the latter may be caused by changes in muscle fiber composition as shown in the soleus. In cross sections of the soleus of Gas7-deficient mice, gross morphological features and levels of myosin heavy chain I (MHC I) and MHC II markers revealed significantly fewer fast fibers. In addition, we found that nerve terminal sprouting, which may be associated with slow and fast muscle fiber composition, was considerably reduced at neuromuscular junctions (NMJ) during aging.
CONCLUSIONS/SIGNIFICANCE: These findings indicate that Gas7 is involved in motor neuron function associated with muscle strength maintenance.
生长停滞特异性基因 7(Gas7)先前被证明参与体外突起的生长;然而,其实际作用仍有待确定。为了研究 Gas7 在体内的生理功能,我们在此生成了一种 Gas7 缺陷型小鼠品系,其具有不稳定的 Gas7 突变蛋白,其功能与野生型 Gas7 相似。
方法/主要发现:我们的数据表明,年老的 Gas7 缺陷型小鼠由于脊髓运动神经元数量减少和肌肉力量下降而出现运动活动缺陷,后者可能是由于腓肠肌中肌纤维组成的变化引起的。在 Gas7 缺陷型小鼠的腓肠肌横切面上,肌球蛋白重链 I(MHC I)和 MHC II 标志物的大体形态特征和水平显示出明显较少的快纤维。此外,我们发现神经末梢发芽在老化过程中在神经肌肉接头(NMJ)处明显减少,这可能与慢肌和快肌纤维组成有关。
结论/意义:这些发现表明 Gas7 参与与肌肉力量维持相关的运动神经元功能。