title: Definition of the unique human extraocular muscle allotype by expression profiling.
abstract: 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 a differential response to diseases; however, this has been attributed to a unique, group-specific pattern of gene expression 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. Three hundred thirty-eight genes were found to be differentially expressed in EOM compared with 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) and high neural, vascular, and mitochondrial content, suggesting that 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 into how human EOMs achieve their unique structural, metabolic, and pathophysiological properties.
authors.affiliation: Department of Physiology and Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6085, USA.
authors.forename: M Dominik
authors.initials: MD
authors.lastname: Fischer
authors.forename: Murat T
authors.initials: MT
authors.lastname: Budak
authors.forename: Marina
authors.initials: M
authors.lastname: Bakay
authors.forename: J Rafael
authors.initials: JR
authors.lastname: Gorospe
authors.forename: D
authors.initials: D
authors.lastname: Kjellgren
authors.forename: F
authors.initials: F
authors.lastname: Pedrosa-Domellöf
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: Tejvir S
authors.initials: TS
authors.lastname: Khurana
mesh_terms: D000293:Adolescent; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005121:Extremities; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005821:Genetic Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009132:Muscles / Q000378:metabolism* / Q000473:pathology*; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D009801:Oculomotor Muscles / Q000378:metabolism* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C510866:MYH13 protein, human; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D012313:RNA; D018995:Myosin Heavy Chains