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Physiol. Genomics (April 26, 2005). doi:10.1152/physiolgenomics.00158.2004 Free Article
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Submitted on July 23, 2004
Accepted on April 20, 2005

Definition of the unique human extraocular muscle allotype by expression profiling

M. Dominik Fischer1, Murat T Budak2, Marina Bakay3, J. Rafael Gorospe3, D. Kjellgren4, F. Pedrosa-Domellof4, Eric P Hoffman3, and Tejvir S Khurana2*

1 Department of Physiology & Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Faculty of Medicine, Witten/Herdecke University, Witten, Germany
2 Department of Physiology & Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
3 Research Center for Genetic Medicine, Children's National Medical Center, George Washington University, Washington, DC, USA
4 Departments of Integrative Medical Biology, Section of Anatomy and Clinical Sciences, Ophthalmology, Umea University, Umea, Sweden

* To whom correspondence should be addressed. E-mail: tsk{at}mail.med.upenn.edu.

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.




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