Skeletal muscle fibers are defined by patterned covariation of key traits t
hat determine contractile and metabolic characteristics. Although the funct
ional properties of most skeletal muscles result from their proportional co
ntent of a few conserved muscle fiber types, some, typically craniofacial,
muscles exhibit fiber types that appear to lie outside the common phenotypi
c range. We analyzed gene expression profiles of three putative muscle clas
ses, limb, masticatory, and extraocular muscle (EOM), in adult mice by high
-density oligonucleotide arrays. Pairwise comparisons using conservative ac
ceptance criteria identified expression differences in 287 genes between EO
M and limb and/or masticatory muscles. Use of significance analysis of micr
oarrays methodology identified up to 400 genes as having an EOM-specific ex
pression pattern. Genes differentially expressed in EOM reflect key aspects
of muscle biology, including transcriptional regulation, sarcomeric organi
zation, excitation-contraction coupling, intermediary metabolism, and immun
e 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.