Unconventional gene therapy holds promise for muscle disease

Abstract

About half of all congenital muscular dystrophies in the western world are caused by mutations in the laminin α2 chain. Mouse models for this disease exist in the form of the dy and dy2j mice as well as knockout mice lacking the laminin α2 chain. In the muscle of these mice, the laminin α4 chain (which normally is expressed in the muscle sarcolemmal basement membrane during the fetal period) is upregulated when the α2 chain is defective. Integrins and the dystroglycan complex are receptors for laminins. The laminin α4 chain lacks the short arm needed for laminin polymerization but contains integrin and low-affinity dystroglycan binding sites. Another molecule that binds to both the laminin α4 chain and dystroglycan is agrin. In an elegant paper, Moll and colleagues1 show that the dystrophic phenotype of laminin α2-deficient mice is partly ameliorated by expressing an agrin minigene.