Unraveling the pathogenesis and development of therapeutic strategies for Fukuyama congenital muscular dystrophy using model animals

Abstract

Fukuyama congenital muscular dystrophy is an autosomal recessive disease that is characterized by congenital muscular dystrophy with abnormalities in central nervous system and/or cardiomyopathy. The responsible gene is Fukutin and its mutations lead to abnormal glycosylation of dystroglycan, a receptor for matrix proteins. We identified a novel post–translational moiety in the sugar chain of dystroglycan, namely, tandemly–connected ribitol–phosphate, and showed that Fukutin encodes an enzyme synthesizing the ribitol–phosphate moiety. Furthermore, we have revealed the pathogenesis how glycosylation defects cause muscular dystrophy, central nervous system abnormalities, and cardiomyopathy using Fukutin conditional knock out mice. In this report, we summarize structure of dystroglycan sugar chain and enzymes responsible for its biosynthesis. We also discuss therapeutic strategies for Fukuyama congenital muscular dystrophy and related diseases.