Muscles of a different 'color'

Much of our knowledge of the responsiveness of skeletal muscle to neurogenic or myogenic disease is based on information obtained from a limb muscle prototype. Disease states interact with well-characterized skeletal muscle fiber types to produce patterned pathologic changes in muscle biopsies that are reliably used in diagnosis. By contrast, some muscle groups exhibit fundamental departures in both structure and function from the limb muscle prototype. Muscle fiber type differences that have been so clearly defined by a concept as simple as "color" (i.e., red, intermediate, and white) suddenly are not so easily resolved. The atypical fiber types might more appropriately be described as gray in color to denote a rather confusing array of characteristics in these unique muscles. The classically defined neurogenic and myogenic muscle signs either may be accentuated or may not always be present and thus may not be of the same diagnostic value for such muscles. Hoh et al ^[1] coined the term allotype to identify such fundamentally distinct muscle classes. To date, the identified skeletal muscle allotypes include limb/diaphragm, masticatory, and extraocular muscle. Other muscles that have not been fully characterized (e.g., laryngeal muscles and muscles of the middle ear) also may prove to be distinct allotypes. Many of the allotype-specific properties have their origin in muscle precursor cell lineage differences. Although epigenetic factors (e.g., innervation, hormonal influences, local cues) may influence the fiber type characteristics within an allotype, extrinsic regulatory events cannot account for differences in phenotypic options that are available across allotypes. Because disease may differentially involve one allotype while sparing one or more of the others, it is important to understand both the structural and functional differences that exist across allotypes as well as the mechanisms that may protect or predispose a particular allotype to disease. In this review, we focus on …