Extraocular muscle is defined by a fundamentally distinct gene expression profile

Abstract

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.

Figure 1

Muscle group-specific differences in gene expression identified by using the Affymetrix algorithm. Frequency distribution histogram illustrating distribution of average fold differences for genes expressed in comparisons between EOM, leg, and jaw muscle groups. Only genes consistently reported as increased, decreased, or no change in all intermuscle group comparisons were plotted. Genes not reaching significance fall in the ± 2 bins.

Figure 2

Muscle group differences in carbohydrate metabolism. Alterations in expression patterns of genes known to participate in glycolysis, gluconeogenesis, glycogen synthesis and catabolism, and glycerol metabolism were mapped onto metabolic pathways. GLUT4, solute carrier family 2 (facilitated glucose transporter), member 4; GLUT1, solute carrier family 2 (facilitated glucose transporter), member 1; G6pt1, glucose-6-phosphatase, transport protein 1; PGM, phosphoglucomutase; Gly Syn, glycogen synthase; Gly Phos, glycogen phosphorylase; Phak1, Phosphorylase kinase alpha 1; Phkb, phosphorylase kinase β; Phkg, phosphorylase kinase gamma; Calm, calmodulin; glu 6-P isomerase, glucose 6-phosphate isomerase; Pkffb, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase; fru 2,6-P, fructose 2,6-bisphospate; glyceraldehyde 3-P DH, glyceraldehyde 3-phosphate dehydrogenase; glycerol 3-P DH, glycerol 3-phosphate dehydrogenase; TPI, triose phosphate isomerase; PK, pyruvate kinase; LDH (B), lactic dehydrogenase, type B; pyrl Cxl, pyruvate carboxylase; pep CK, phosphoenolpyruvate carboxykinase; fruc 6-Pase, fructose 6-phosphotase.