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.
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Acknowledgments
We thank Dr. Paul Schimmel (Scripps Research Institute; La Jolla, CA) for kindly providing the WT and G240R mutant GARS clones. This work was supported by a Global Frontier Project Grant (2012M3A6A2011-0032149) from the National Research Foundation funded by the Ministry of Education, Science and Technology of Korea and a National Research Foundation of Korea (NRF) Grant funded by the Korean government (MEST; No. 20120009380).
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Ah Jung Seo and Youn Ho Shin have contributed equally to this work.
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Seo, A.J., Shin, Y.H., Lee, S.J. et al. A novel adenoviral vector-mediated mouse model of Charcot-Marie-Tooth type 2D (CMT2D). J Mol Hist 45, 121–128 (2014). https://doi.org/10.1007/s10735-013-9537-0
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DOI: https://doi.org/10.1007/s10735-013-9537-0