Expression profiling reveals metabolic and structural components of extraocular muscles.
The extraocular muscles (EOM) are anatomically and physiologically distinct from other skeletal muscles. EOM are preferentially affected in mitochondrial myopathies, but spared in Duchenne's muscular dystrophy. The anatomical and pathophysiological properties of EOM have been attributed to their unique molecular makeup: an allotype. We used expression profiling to define molecular features of the EOM allotype. We found 346 differentially expressed genes in rat EOM compared with tibialis anterior, based on a twofold difference cutoff. Genes required for efficient, fatigue-resistant, oxidative metabolism were increased in EOM, whereas genes for glycogen metabolism were decreased. EOM also showed increased expression of genes related to structural components of EOM such as vessels, nerves, mitochondria, and neuromuscular junctions. Additionally, genes related to specialized functional roles of EOM such as the embryonic and EOM-specific myosin heavy chains and genes for muscle growth, development, and/or regeneration were increased. The EOM expression profile was validated using biochemical, structural, and molecular methods. Characterization of the EOM expression profile begins to define gene transcription patterns associated with the unique anatomical, metabolic, and pathophysiological properties of EOM.
Fischer
M Dominik
MD
Department of Physiology and Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Gorospe
J Rafael
JR
Felder
Edward
E
Bogdanovich
Sasha
S
Pedrosa-Domellöf
F
F
Ahima
Rexford S
RS
Rubinstein
Neal A
NA
Hoffman
Eric P
EP
Khurana
Tejvir S
TS
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D018482:Muscle, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism; D009801:Oculomotor Muscles / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013977:Tibia
D000975:Antioxidants; D002118:Calcium