Motor unit abnormalities in Dystonia musculorum mice

PLoS One. 2011;6(6):e21093. doi: 10.1371/journal.pone.0021093. Epub 2011 Jun 15.

Abstract

Dystonia musculorum (dt) is a mouse inherited sensory neuropathy caused by mutations in the dystonin gene. While the primary pathology lies in the sensory neurons of dt mice, the overt movement disorder suggests motor neurons may also be affected. Here, we report on the contribution of motor neurons to the pathology in dt(27J) mice. Phenotypic dt(27J) mice display reduced alpha motor neuron cell number and eccentric alpha motor nuclei in the ventral horn of the lumbar L1 spinal cord region. A dramatic reduction in the total number of motor axons in the ventral root of postnatal day 15 dt(27J) mice was also evident. Moreover, analysis of the trigeminal nerve of the brainstem showed a 2.4 fold increase in number of degenerating neurons coupled with a decrease in motor neuron number relative to wild type. Aberrant phosphorylation of neurofilaments in the perikaryon region and axonal swellings within the pre-synaptic terminal region of motor neurons were observed. Furthermore, neuromuscular junction staining of dt(27J) mouse extensor digitorum longus and tibialis anterior muscle fibers showed immature endplates and a significant decrease in axon branching compared to wild type littermates. Muscle atrophy was also observed in dt(27J) muscle. Ultrastructure analysis revealed amyelinated motor axons in the ventral root of the spinal nerve, suggesting a possible defect in Schwann cells. Finally, behavioral analysis identified defective motor function in dt(27J) mice. This study reveals neuromuscular defects that likely contribute to the dt(27J) pathology and identifies a critical role for dystonin outside of sensory neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Brain Stem / pathology
  • Brain Stem / physiopathology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • DNA Primers
  • Dystonia Musculorum Deformans / physiopathology*
  • Dystonin
  • Fluorescent Antibody Technique
  • Mice
  • Microscopy, Electron
  • Motor Neurons / pathology*
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Phosphorylation
  • Spinal Cord / pathology
  • Spinal Cord / physiopathology

Substances

  • Carrier Proteins
  • Cytoskeletal Proteins
  • DNA Primers
  • Dst protein, mouse
  • Dystonin
  • Nerve Tissue Proteins