Extraocular muscle is defined by a fundamentally distinct gene expression profile

Skeletal muscle fibers are defined by patterned covariation of key traits that determine contractile and metabolic characteristics. Although the functional properties of most skeletal muscles result from their proportional content of a few conserved muscle fiber types, some, typically craniofacial, muscles exhibit fiber types that appear to lie outside the common phenotypic range. We analyzed gene expression profiles of three putative muscle classes, limb, masticatory, and extraocular muscle (EOM), in adult mice by high-density oligonucleotide arrays. Pairwise comparisons using conservative acceptance criteria identified expression differences in 287 genes between EOM and limb and/or masticatory muscles. Use of significance analysis of microarrays methodology identified up to 400 genes as having an EOM-specific expression pattern. Genes differentially expressed in EOM reflect key aspects of muscle biology, including transcriptional regulation, sarcomeric organization, excitation-contraction coupling, intermediary metabolism, and immune response. These patterned differences in gene expression define EOM as a distinct muscle class and may explain the unique response of these muscles in neuromuscular diseases.

骨骼肌纤维由决定其收缩性能与代谢特征的关键性状的模式化共变异所界定。尽管多数骨骼肌的功能特性由其所含几种保守型肌纤维类型的比例所决定，但部分肌肉——典型如颅面肌——所呈现的肌纤维类型似乎超出了常见的表型范围。本研究采用高密度寡核苷酸芯片技术，对成年小鼠三类推定的肌肉类别——肢肌、咀嚼肌以及眼外肌（extraocular muscle, EOM）——的基因表达谱进行了分析。采用保守的显著性判定标准进行两两比较，结果显示眼外肌与肢肌和/或咀嚼肌之间存在287个差异表达基因。借助微阵列显著性分析（significance analysis of microarrays）方法，可鉴定出多达400个具有眼外肌特异性表达模式的基因。眼外肌中差异表达的基因反映了肌肉生物学的多个关键方面，包括转录调控、肌节结构、兴奋-收缩耦联、中间代谢以及免疫应答。这些模式化的基因表达差异将眼外肌界定为一类独特的肌肉类别，同时也可解释此类肌肉在神经肌肉疾病中呈现的独特应答特征。