Dystrophin-deficient zebrafish feature aspects of the Duchenne muscular dystrophy pathology
Dystrophin-deficient zebrafish feature aspects of the Duchenne muscular dystrophy pathology
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DOI：
10.1016/j.nmd.2010.08.004
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发表时间：
2010-12-01
影响因子：
2.8
通讯作者：
Currie, Peter D.
中科院分区：
文献类型：
--
作者：
Berger, Joachim;Berger, Silke;Currie, Peter D.
Duchenne肌营养不良症是由肌营养不良蛋白基因突变引起的。在人类中，斑马鱼肌营养不良蛋白最初在邻近肌腱连接处的肌纤维的外周末端表达，并逐渐转移到非连接部位。肌营养不良蛋白缺陷的斑马鱼幼虫的特征是大量坏死的纤维被单核浸润性广泛纤维化所取代，伴有炎症和肌纤维交叉的更广泛变化。截面积肌祖细胞增殖不能补偿广泛的骨骼肌损失肌营养不良蛋白缺陷斑马鱼幼虫的实时成像记录了肌肉收缩引起的肌纤维分离。缺陷型斑马鱼与人类疾病的许多方面相似，这表明斑马鱼模型系统的特定优点，例如进行体内药物筛选和真实的肌纤维损失的时间分析可用于了解和治疗肌营养不良蛋白缺陷型肌营养不良症的病理基础相关的新见解（C）2010 Elsevier B V版权所有
Duchenne muscular dystrophy is caused by mutations in the dystrophin gene As in humans zebrafish dystrophin is initially expressed at the peripheral ends of the myofibres adjacent to the myotendinous Junction and gradually shifts to non-junctional sites Dystrophin-deficient zebrafish larvae are characterised by abundant necrotic fibres being replaced by mono-nucleated infiltrates extensive fibrosis accompanied by inflammation and a broader variation in muscle fibre cross-sectional areas Muscle progenitor proliferation cannot compensate for the extensive skeletal muscle loss Live imaging of dystrophin-deficient zebrafish larvae documents detaching myofibres elicited by muscle contraction Correspondingly the progressive phenotype of dystrophin-deficient zebrafish resembles many aspects of the human disease suggesting that specific advantages of the zebrafish model system such as the ability to undertake in vivo drug screens and real time analysis of muscle fibre loss could be used to make novel insights relevant to understanding and treating the pathological basis of dystrophin-deficient muscular dystrophy (C) 2010 Elsevier B V All rights reserved