title: GRS defective axonal distribution as a potential contributor to distal spinal muscular atrophy type V pathogenesis in a new model of GRS-associated neuropathy.
abstract: Distal spinal muscular atrophy type V (dSMA-V), a hereditary axonal neuropathy, is a glycyl-tRNA synthetase (GRS)-associated neuropathy caused by a mutation in GRS. In this study, using an adenovirus vector system equipped with a neuron-specific promoter, we constructed a new GRS-associated neuropathy mouse model. We found that wild-type GRS (WT) is distributed in peripheral axons, dorsal root ganglion (DRG) cell bodies, central axon terminals and motor neuron cell bodies in the mouse model. In contrast, the L129P mutant GRS was localized in DRG and motor neuron cell bodies. Thus, we propose that the disease-causing L129P mutant is linked to a distribution defect in peripheral nerves in vivo.
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Biomedical Science Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Ah Jung
authors.initials: AJ
authors.lastname: Seo
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Biomedical Science Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Byung Sun
authors.initials: BS
authors.lastname: Park
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Biomedical Science Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: jjung@khu.ac.kr.
authors.forename: Junyang
authors.initials: J
authors.lastname: Jung
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors; D006032:Glycine-tRNA Ligase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology*
chemical_list: D006032:Glycine-tRNA Ligase
keywords: Axonal degeneration; Glycyl-tRNA synthetase; Recombinant adenovirus; Spinal muscular atrophy