The influence of muscle type and dystrophin deficiency on murine expression profiles
The influence of muscle type and dystrophin deficiency on murine expression profiles
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DOI：
10.1007/s00335-005-0053-8
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发表时间：
2005-10-01
期刊：
影响因子：
2.5
通讯作者：
Kunkel, LM
中科院分区：
文献类型：
--
作者：
Haslett, JN;Kang, PB;Kunkel, LM
Duchenne肌营养不良症患者、mdx小鼠和mdx(5CV)小鼠之间的表型差异表明，尽管dystrophin缺乏的共同病因，次级机制对表型严重程度有很大影响。不同骨骼肌对肌营养不良蛋白缺乏的不同反应支持这一假说。为了探索这些差异，从野生型、MDX和MDX(5CV)小鼠的六种不同的骨骼肌(横隔肌、比目鱼肌、腓肠肌、股四头肌、胫前肌和指长伸肌)提取的重复RNA靶标生成了基因表达谱，得到了18个肌肉样本的36个数据集。这些数据集以三种不同的方式进行比较：(1)仅在野生型样本之间进行比较；(2)在所有36个数据集中进行比较；(3)在每种肌肉类型的菌株之间进行比较。比目鱼肌和横隔肌的分子谱与其他四种肌肉类型以及彼此之间有显著的分离。纤维类型的比例可以解释其中的一些差异。野生型基因表达谱的这些差异也可能反映了骨骼肌之间存在的生物力学差异。进一步探索最能区分这些肌肉的基因可能有助于解释生物力学差异的起源，以及为什么一些肌肉比其他肌肉更能抵抗肌营养不良蛋白缺乏的原因。
The phenotypic differences among Duchenne muscular dystrophy patients, mdx mice, and mdx(5cv) mice suggest that despite the common etiology of dystrophin deficiency, secondary mechanisms have a substantial influence on phenotypic severity. The differential response of various skeletal muscles to dystrophin deficiency supports this hypothesis. To explore these differences, gene expression profiles were generated from duplicate RNA targets extracted from six different skeletal muscles (diaphragm, soleus, gastrocnemius, quadriceps, tibialis anterior, and extensor digitorum longus) from wildtype, mdx, and mdx(5cv) mice, resulting in 36 data sets for 18 muscle samples. The data sets were compared in three different ways: (1) among wild-type samples only, (2) among all 36 data sets, and (3) between strains for each muscle type. The molecular profiles of soleus and diaphragm separate significantly from the other four muscle types and from each other. Fiber-type proportions can explain some of these differences. These variations in wild-type gene expression profiles may also reflect biomechanical differences known to exist among skeletal muscles. Further exploration of the genes that most distinguish these muscles may help explain the origins of the biomechanical differences and the reasons why some muscles are more resistant than others to dystrophin deficiency.