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 and͞or 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.

Real-time PCR provides evidence for thyrotropin receptor mRNA expression in orbital as well as in extraorbital tissues

“…The authors concluded that the expression of this receptor in TAO may be induced in vivo by a humoral factor not present in the cell culture environment (12,13). Recently, gene expression profiles in extraocular muscles in adult mice by high-density oligonucleotide arrays were analyzed (18). The use of significance analysis of microarray methodology identified up to 400 genes as having an extraocular-specific expression pattern and the TSHr was not shown (18).…”

Functional and Genomic Changes in the Mouse Ocular Motor System in Response to Light Deprivation from Birth

“…High-density oligonucleotide microarray studies were conducted as described earlier (Porter et al, 2001). Briefly, total RNA was obtained from oculomotor nuclei isolated from control and light-deprived mice with Trizol reagent (Invitrogen, San Diego, CA) by following the manufacturer's protocol; nuclei from four to five animals were combined into each independent total RNA sample to lessen the effect of inter-subject variability.…”

Effect of complement and its regulation on myasthenia gravis pathogenesis

“…As mentioned previously, the EOM are particularly susceptible to MG [76], and murine EOM have been found to have low expression levels of the cell surface regulators compared with other skeletal muscles and when EAMG was induced [34,35]. Coupling studies that indicate that deficiency of complement regulators increase EAMG disease severity and that EOM has low levels of these regulators would suggest that EOM is susceptible to MG because of intrinsic low levels of local complement inhibition.…”

“…The properties that may mediate this susceptibility include antibody targets, the immune response and the safety factor of the extraocular muscle (EOM) neuromuscular junctions. Recently, a relative lack of intrinsic complement regulator has been identified in EOM [34,35] and this may prove to be a major contributor to EOM susceptibility to MG.…”