Fischer MD, Budak MT, Bakay M, Gorospe JR, Kjellgren D, Pedrosa-Domellof F, Hoffman EP, Khurana TS.
The extraocular muscles (EOMs) are a unique group of specialized muscles that are anatomically and physiologically distinct from other skeletal muscles. Perhaps the most striking characteristic of the EOMs is their differential sensitivity to disease. EOMs are spared in Duchenne's muscular dystrophy (DMD), despite widespread involvement of other skeletal muscles. Conversely, they are early and prominent targets in myasthenia gravis and mitochondrial myopathies. It is unclear how EOMs achieve such specialization or differential response to diseases, however, this has been attributed to a unique, group-specific pattern of geneexpression or "allotype". To begin to address these issues as well as define the human EOM allotype, we analyzed the human EOM transcriptome using oligonucleotide-based expression profiling. 338 genes were found to be differentially expressed in EOM compared to Quadriceps femoris limb muscle, using a twofold cutoff. Functional characterization revealed expression patterns corresponding to known metabolic and structural properties of EOMs such as expression of EOM-specific myosin heavy chain (MYH13), high neural, vascular and mitochondrial content, suggesting the profiling was sensitive and specific. Genes related to myogenesis, stem cells and apoptosis were detected at high levels in normal human EOMs, suggesting that efficient and continuous regeneration and/or myogenesis may be a mechanism by which the EOMs remain clinically and pathologically spared in diseases such as DMD. Taken together, this study provides insight of how human EOMs achieve their unique structural, metabolic and patho-physiological properties.
眼外肌是一组在解剖和生理上都与其他骨骼肌不同的特殊肌肉，其中各块肌肉对疾病的受累敏感性有所不同。在杜兴型肌营养不良症中眼外肌不受累，然而在重症肌无力和线粒体肌病中又首当其冲。目前不清楚为何眼外肌在不同疾病中受累情况不同，有人认为可能与同种异型基因表达有关。为确定人类眼外肌的同种异型基因表达，Fischer等分析了人类眼外肌的转录情况，发现有338个基因在眼外肌和股四头肌中的表达有差异，其中不乏一些代谢性和结构性的基因，如眼外肌特异性肌球蛋白重链(MYH13)、血管和线粒体成分的相关基因等。与肌肉形成、干细胞和凋亡有关的基因在正常眼外肌中有较高表达，提示眼外肌中有充分的肌肉再生或形成，可能可以解释为何在杜兴型肌营养不良症中为何不受累。
Physiol Genomics. 2005 Apr 26
