title: Repression of nuclear CELF activity can rescue CELF-regulated alternative splicing defects in skeletal muscle models of myotonic dystrophy.
abstract: Myotonic dystrophy type 1 (DM1) is caused by the expansion of CUG repeats in the 3' UTR of DMPK transcripts. DM1 pathogenesis has been attributed in part to alternative splicing dysregulation via elevation of CUG-BP, Elav-like family member 1 (CELF1). Several therapeutic approaches have been tested in cells and mice, but no previous studies had specifically targeted CELF1. Here, we show that repressing CELF activity rescues CELF-dependent alternative splicing in cell culture and transgenic mouse models of DM1. CELF-independent splicing, however, remained dysregulated. These data highlight both the potential and limitations of targeting CELF1 for the treatment of DM1.
authors.affiliation: Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave. NC10, Cleveland, OH 44195 USA.
authors.forename: Dara S
authors.initials: DS
authors.lastname: Berger
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Ladd