title: A novel adenoviral vector-mediated mouse model of Charcot-Marie-Tooth type 2D (CMT2D).
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.
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Heogi-Dong 1, Dongdaemun-Gu, Seoul, 130-701, Republic of Korea.
authors.forename: Ah Jung
authors.initials: AJ
authors.lastname: Seo
authors.forename: Youn Ho
authors.initials: YH
authors.lastname: Shin
authors.forename: Seo Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Doyeun
authors.initials: D
authors.lastname: Kim
authors.forename: Byung Sun
authors.initials: BS
authors.lastname: Park
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.forename: Kyu Ha
authors.initials: KH
authors.lastname: Choi
authors.forename: Na Young
authors.initials: NY
authors.lastname: Jeong
authors.forename: Chan
authors.initials: C
authors.lastname: Park
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Jang
authors.forename: Youngbuhm
authors.initials: Y
authors.lastname: Huh
authors.forename: Junyang
authors.initials: J
authors.lastname: Jung
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001369:Axons / Q000201:enzymology; D002607:Charcot-Marie-Tooth Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000201:enzymology / Q000473:pathology; D005822:Genetic Vectors; D006032:Glycine-tRNA Ligase / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000201:enzymology; D020125:Mutation, Missense; D009413:Nerve Fibers, Myelinated / Q000201:enzymology; D009928:Organ Specificity; D010525:Peripheral Nerves / Q000201:enzymology / Q000473:pathology
chemical_list: D006032:Glycine-tRNA Ligase