Altered Fiber Types in Regenerated Muscle of Fktn‐KO Muscular Dystrophy Mice

Abstract

Secondary dystroglycanopathies are a class of muscular dystrophy caused by mutations in genes, including fukutin (FKTN), that are important for the glycosylation of alpha‐dystroglycan (aDG). Loss of glycosylation disrupts aDG binding to laminin, causing defects in muscle and nervous tissues. To assess the role of aDG in fiber type specification of regenerating muscle, we compared muscle fiber types 14 days after toxin injury in skeletal muscle‐specific (Myf5, developmental) and whole animal, post‐development‐induced (TAM) models of Fktn deficiency (KO) at equivalent times post‐gene deletion. Embryonic myosin heavy chain‐expressing fibers, an early regeneration marker, were increased in TAM‐Fktn KO mice 14 days after injury, suggesting that aDG disruption may delay muscle differentiation in this model. Oxidative fibers (type 1 and type 2A) were increased after injury in the TAM‐Fktn KO compared to Myf5‐Fktn KO mice. Type 2X fibers were reduced in toxin regenerated muscle compared to vehicle‐treated muscle for all study groups except the Myf5‐Fktn KO mice. Instead, Myf5‐Fktn KO showed a trend towards fewer type 2X fibers on the uninjured side. These data suggest that aDG contributes to skeletal muscle maturation and fiber type specification in a manner that may be timing and/or location dependent.