Muscle glycogen phosphorylase (PYGM) is a key enzyme in the first step of glycogenolysis. Mutation in the PYGM gene leads to autosomal recessive McArdle disease. Patients suffer from exercise intolerance with premature fatigue, muscle cramps and myalgia due to lack of available glucose in muscles. So far, no efficient treatment has been found. The zebrafish has many experimental advantages, and was successfully implemented as an animal model of human myopathies. Since zebrafish skeletal muscles share high similarity with human skeletal muscles, it is our animal of choice to investigate the impact of Pygm knockdown on skeletal muscle tissue. The two forms of the zebrafish enzyme, Pygma and Pygmb, share more than 80% amino acid sequence identity with human PYGM. We show that the Pygm level varies at both the mRNA and protein level in distinct stages of zebrafish development, which is correlated with glycogen level. The Pygm distribution in muscles varies from dispersed to highly organized at 72 hpf. The pygma and pygmb morpholino knockdown resulted in a reduced Pygm level in zebrafish morphants, which exhibited altered, disintegrated muscle structure and accumulation of glycogen granules in the subsarcolemmal region. Thus, lowering the Pygm level in zebrafish larvae leads to an elevated glycogen level and to morphological muscle changes mimicking the symptoms of human McArdle disease. The zebrafish model of this human disease might contribute to further understanding of its molecular mechanisms and to the development of appropriate treatment.

肌肉糖原磷酸化酶（PYGM）是糖原分解第一步中的关键酶。PYGM基因突变会导致常染色体隐性遗传性McArdle病。由于肌肉中缺乏可用的葡萄糖，患者患有运动不耐力，过早疲劳，肌肉痉挛和肌痛。迄今为止，尚未发现有效的治疗方法。斑马鱼具有许多实验优势，并已成功实施为人类肌病的动物模型。由于斑马鱼的骨骼肌与人类的骨骼肌具有高度相似性，因此研究Pygm的影响是我们的首选动物击倒骨骼肌组织。斑马鱼酶的两种形式（Pygma和Pygmb）与人PYGM的氨基酸序列同一性超过80％。我们显示在斑马鱼发育的不同阶段，Pygm水平在mRNA和蛋白质水平上均发生变化，这与糖原水平相关。肌肉中的Pygm分布在72 hpf时从分散到高度有组织。该pygma和pygmb吗啉代敲低导致斑马鱼吗啡的Pygm水平降低，斑马鱼的吗啡呈现出改变的，分解的肌肉结构和糖原颗粒在肌膜下区域的积累。因此，降低斑马鱼幼虫的Pygm水平会导致糖原水平升高，并导致模仿人类McArdle疾病症状的肌肉形态改变。这种人类疾病的斑马鱼模型可能有助于进一步了解其分子机制并开发适当的治疗方法。