Genetic defects in muscular dystrophy

The muscular dystrophies are a group of neuromuscular disorders associated with muscle weakness and wasting, which in many forms can lead to loss of ambulation and premature death. A number of muscular dystrophies are associated with loss of proteins required for the maintenance of muscle membrane integrity, in particular with proteins that comprise the dystrophin-associated glycoprotein (DAG) complex. Proper glycosylation of O-linked mannose chains on alpha-dystroglycan, a DAG member, is required for the binding of the extracellular matrix to dystroglycan and for proper DAG function. A number of congenital disorders of glycosylation have now been described where alpha-dystroglycan glycosylation is altered and where muscular dystrophy is a predominant phenotype. Glycosylation is also increasingly being appreciated as a genetic modifier of disease phenotypes in many forms of muscular dystrophy and as a target for the development of new therapies. Here we will review the mouse models available for the study of this group of diseases and outline the methodologies required to describe disease phenotypes.