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

• Published in: Journal of molecular histology Vol. 45; no. 2; pp. 121 - 128
• Main Authors: Seo, Ah Jung, Shin, Youn Ho, Lee, Seo Jin, Kim, Doyeun, Park, Byung Sun, Kim, Sunghoon, Choi, Kyu Ha, Jeong, Na Young, Park, Chan, Jang, Ji-Yeon, Huh, Youngbuhm, Jung, Junyang
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.04.2014; Springer Nature B.V
• Subjects: Adenoviridae - genetics; Animals; Axons - enzymology; Biomedical and Life Sciences; Biomedicine; Cell Biology; Charcot-Marie-Tooth Disease - enzymology; Charcot-Marie-Tooth Disease - genetics; Charcot-Marie-Tooth Disease - pathology; Developmental Biology; Disease Models, Animal; Ganglia, Spinal - enzymology; Ganglia, Spinal - pathology; Genetic Vectors; Glycine-tRNA Ligase - genetics; Glycine-tRNA Ligase - metabolism; Life Sciences; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motor Neurons - enzymology; Mutation, Missense; Nerve Fibers, Myelinated - enzymology; Organ Specificity; Peripheral Nerves - enzymology; Peripheral Nerves - pathology; Short Communication; Recombinant adenovirus; Glycyl-tRNA synthetase; Demyelination; Charcot-Marie-Tooth disease; Axonal degeneration
• ISSN: 1567-2379; 1567-2387
• DOI: 10.1007/s10735-013-9537-0

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.