A novel adenoviral vector-mediated mouse model of Charcot-Marie-Tooth type 2D (CMT2D)

J Mol Histol. 2014 Apr;45(2):121-8. doi: 10.1007/s10735-013-9537-0. Epub 2013 Aug 30.

Abstract

Charcot-Marie-Tooth disease type 2D is a hereditary axonal and glycyl-tRNA synthetase (GARS)-associated neuropathy that is caused by a mutation in GARS. Here, we report a novel GARS-associated mouse neuropathy model using an adenoviral vector system that contains a neuronal-specific promoter. In this model, we found that wild-type GARS is distributed to peripheral axons, dorsal root ganglion (DRG) cell bodies, central axon terminals, and motor neuron cell bodies. In contrast, GARS containing a G240R mutation was localized in DRG and motor neuron cell bodies, but not axonal regions, in vivo. Thus, our data suggest that the disease-causing G240R mutation may result in a distribution defect of GARS in peripheral nerves in vivo. Furthermore, a distributional defect may be associated with axonal degradation in GARS-associated neuropathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Axons / enzymology
  • Charcot-Marie-Tooth Disease / enzymology*
  • Charcot-Marie-Tooth Disease / genetics
  • Charcot-Marie-Tooth Disease / pathology
  • Disease Models, Animal
  • Ganglia, Spinal / enzymology
  • Ganglia, Spinal / pathology
  • Genetic Vectors
  • Glycine-tRNA Ligase / genetics
  • Glycine-tRNA Ligase / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Neurons / enzymology
  • Mutation, Missense
  • Nerve Fibers, Myelinated / enzymology
  • Organ Specificity
  • Peripheral Nerves / enzymology
  • Peripheral Nerves / pathology

Substances

  • Glycine-tRNA Ligase