Global/temporal gene expression in diaphragm and hindlimb muscles of dystrophin-deficient (mdx) mice
Global/temporal gene expression in diaphragm and hindlimb muscles of dystrophin-deficient (mdx) mice
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DOI：
10.1152/ajpcell.00112.2002
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发表时间：
2002-09-01
影响因子：
5.5
通讯作者：
Leger, JJ
中科院分区：
文献类型：
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作者：
Rouger, K;Le Cunff, M;Leger, JJ
mdx小鼠是人杜氏肌营养不良（DMD）的模型，DMD是一种X连锁的骨骼肌组织退行性疾病，其特征在于缺乏肌营养不良蛋白。mdx小鼠表现出比DMD患者温和得多的表型。在生命的第一周后，当所有mdx肌肉都像年轻DMD患者的肌肉一样进化时，mdx后肢肌肉基本上补偿了肌营养不良蛋白的缺乏，而mdx膈肌逐渐受到疾病的影响。我们使用cDNA微阵列比较了1,082个基因的表达谱，这些基因是先前通过减法选择的，在小鼠生命的第一年的12个时间点，在对照组和mdx组后肢和膈肌中。我们确定：1）抗肌萎缩蛋白基因缺陷诱导了112个编码蛋白质的基因的显著表达重塑，这些蛋白质涉及不同的肌肉细胞功能; 2）观察到的三分之二的转录组异常在成年mdx后肢和膈肌之间存在差异。我们的研究结果表明，mdx膈肌和mdx后肢肌肉的进化都不完全像人类DMD肌肉。这一发现应考虑在未来的实验中使用mdx小鼠作为治疗试验的模型的解释。
The mdx mouse is a model for human Duchenne muscular dystrophy (DMD), an X-linked degenerative disease of skeletal muscle tissue characterized by the absence of the dystrophin protein. The mdx mice display a much milder phenotype than DMD patients. After the first week of life when all mdx muscles evolve like muscles of young DMD patients, mdx hindlimb muscles substantially compensate for the lack of dystrophin, whereas mdx diaphragm muscle becomes progressively affected by the disease. We used cDNA microarrays to compare the expression profile of 1,082 genes, previously selected by a subtractive method, in control and mdx hindlimb and diaphragm muscles at 12 time points over the first year of the mouse life. We determined that 1) the dystrophin gene defect induced marked expression remodeling of 112 genes encoding proteins implicated in diverse muscle cell functions and 2) two-thirds of the observed transcriptomal anomalies differed between adult mdx hindlimb and diaphragm muscles. Our results showed that neither mdx diaphram muscle nor mdx hindlimb muscles evolve entirely like the human DMD muscles. This finding should be taken under consideration for the interpretation of future experiments using mdx mice as a model for therapeutic assays.