title: Neuropathic pain model of peripheral neuropathies mediated by mutations of glycyl-tRNA synthetase.
abstract: Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory neuropathy. Previous studies have found that, according to CMT patients, neuropathic pain is an occasional symptom of CMT. However, neuropathic pain is not considered to be a significant symptom associated with CMT and, as a result, no studies have investigated the pathophysiology underlying neuropathic pain in this disorder. Thus, the first animal model of neuropathic pain was developed by our laboratory using an adenovirus vector system to study neuropathic pain in CMT. To this end, glycyl-tRNA synthetase (GARS) fusion proteins with a FLAG-tag (wild type [WT], L129P and G240R mutants) were expressed in spinal cord and dorsal root ganglion (DRG) neurons using adenovirus vectors. It is known that GARS mutants induce GARS axonopathies, including CMT type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V). Additionally, the morphological phenotypes of neuropathic pain in this animal model of GARS-induced pain were assessed using several possible markers of pain (Iba1, pERK1/2) or a marker of injured neurons (ATF3). These results suggest that this animal model of CMT using an adenovirus may provide information regarding CMT as well as a useful strategy for the treatment of neuropathic pain.
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Seo Jin
authors.identifier: 0000-0001-6531-0526
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Ah Jung
authors.identifier: 0000-0002-5211-3213
authors.initials: AJ
authors.lastname: Seo
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Byung Sun
authors.identifier: 0000-0001-6131-6808
authors.initials: BS
authors.lastname: Park
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Hyun Woo
authors.identifier: 0000-0002-8984-8694
authors.initials: HW
authors.lastname: Jo
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Youngbuhm
authors.identifier: 0000-0002-7687-0374
authors.initials: Y
authors.lastname: Huh
mesh_terms: D000818:Animals; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000503:physiopathology*; D004195:Disease Models, Animal; D006032:Glycine-tRNA Ligase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D009437:Neuralgia / Q000175:diagnosis* / Q000503:physiopathology*
chemical_list: D006032:Glycine-tRNA Ligase
keywords: ATF3 Protein Mouse; Adenoviridae; Charcot-Marie-Tooth Disease; Glycyl-tRNA Ligase; Microglia; Neuralgia