title: Peripheral neuropathy is linked to a severe form of myotonic dystrophy in transgenic mice.
abstract: Myotonic dystrophy type 1 (DM1) is a multisystem disorder with a variable phenotype. The involvement of peripheral nerves in DM1 disease is controversial. The DM1 animal model DM300 transgenic mice that carry 350 to 500 CTG repeats express a mild DM1 phenotype but do not exhibit motor or sensory pathology. Here, we investigated the presence or absence of peripheral neuropathy in transgenic mice (DMSXL) that carry more than 1,300 CTG repeats and display a severe form of DM1. Electrophysiologic, histologic, and morphometric methods were used to investigate the structure and function of peripheral nerves. We observed lower compound muscle action potentials recorded from hind limb muscles and slowing of sciatic nerve conduction velocity in DMSXL versus control mice. Morphometric analyses showed an axonopathy and neuronopathy in the DMSXL mice characterized by a decrease in numbers of myelinated motor axons in sciatic nerve and in spinal cord motor neurons. Pathologic alterations in the structure of hind limb neuromuscular junctions were also detected in the DMSXL mice. These results suggest that peripheral neuropathy can be linked to a large CTG expansion and a severe form of DM1.
authors.affiliation: Department of Clinical Neurosciences, University Hospital, Lausanne, Switzerland.
authors.forename: Petrica-Adrian
authors.initials: PA
authors.lastname: Panaite
authors.forename: Marie
authors.initials: M
authors.lastname: Kielar
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kraftsik
authors.forename: Geneviève
authors.initials: G
authors.lastname: Gourdon
authors.forename: Thierry
authors.initials: T
authors.lastname: Kuntzer
authors.forename: Ibtissam
authors.initials: I
authors.lastname: Barakat-Walter
mesh_terms: D000818:Animals; D002038:Bungarotoxins / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004576:Electromyography / Q000379:methods; D019054:Evoked Potentials, Motor / Q000235:genetics / Q000502:physiology; D006614:Hindlimb / Q000473:pathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009223:Myotonic Dystrophy / Q000150:complications* / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology; D016900:Neurofilament Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020426:Sciatic Neuropathy / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: D002038:Bungarotoxins; C585517:DMPK protein, human; C585516:DMPK protein, mouse; D016900:Neurofilament Proteins; C051774:neurofilament protein H; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases