Status of muscle signaling pathways in the early pathogenesis of dystroglycanopathy‐type muscular dystrophy

Abstract

A subset of muscular dystrophies are caused by abnormal glycosylation of α‐dystroglycan. Without its proper sugar structure, α‐dystroglycan binding to extracellular matrix proteins (e.g. laminin, perlecan) is compromised, disrupting the structural integrity of muscle and other tissues. Mutations in the FCMD gene, encoding fukutin, cause severe and milder dystroglycanopathies, Fukuyama congenital muscular dystrophy (FCMD) and limb‐girdle muscular dystrophy type 2M (LGMD 2M), respectively. Using fukutin conditional knockout mice, we have evidence that severe congenital muscular dystrophy phenotypes involve abnormal skeletal muscle development and/or differentiation. We will present a molecular, biochemical and histological approach, screening select muscle signaling pathways in young knockout mice, to identify abnormalities in skeletal muscle development/differentiation. These findings bring new insight to potential mechanisms underlying early disease pathogenesis and severe phenotypic outcomes in dystroglycanopathy‐type congenital muscular dystrophies.This work has been supported by the Muscular Dystrophy Association (Development Grant) and the University of Georgia, College of Pharmacy.