title: Programmed cell death in dystrophic (mdx) muscle is inhibited by IGF-II.
abstract: The pathology of Duchenne Muscular Dystrophy (DMD) is characterised by unstable muscle fibres and by increased cell turnover due to the absence of functional dystrophin protein. We have used skeletal muscle, primary muscle stem cell cultures (Smith and Schofield, 1994; Smith et al., paper submitted) and clonal cell lines of the mouse DMD model (mdx) and its congenic control (C57BI) to demonstrate that programmed cell death (PCD) and apoptotic morphology is increased in dystrophic (mdx) muscle and in cultured muscle cells. We also show that the peptide growth factor (IGF-II), which is thought to play a role in mammalian myogenesis, reduces PCD in mammalian skeletal muscle myoblasts both in vivo and in vitro. This is the first time that apoptosis or PCD have been demonstrated in normal mammalian skeletal muscle. We discuss the potential of this system in determining the role of PCD in mammalian myogenesis and skeletal muscle maturation, its significance in dystrophic muscle, and suggest a novel therapeutic route whereby the pathology of DMD may be alleviated using the survival properties of IGF-II.
authors.affiliation: Department of Anatomy, University of Cambridge, Downing Street, Cambridge, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: G
authors.initials: G
authors.lastname: Fowkes
authors.forename: P N
authors.initials: PN
authors.lastname: Schofield