title: A possible cellular mechanism of neuronal loss in the dorsal root ganglia of Dystonia musculorum (dt) mice.
abstract: Dystonia musculorum (dt) is a mutant mouse with hereditary sensory neuropathy. A defective bullous pemphigoid antigen 1 (BPAG1) gene is responsible for this mutation. In the present study, we examined the distribution of neuronal intermediate filament proteins in the central and peripheral processes of the dorsal root ganglia (DRG) in adult dt mice using different approaches. We found that not only BPAG1, but also alpha-internexin was absent in the DRG neurons in adult dt mice. To study the relationship between the absence of alpha-internexin and the progressive neuronal loss in the DRG of dt mice, we further cultured DRG neurons from embryonic dt mutants. Immunocytochemical assay of cultured DRG neurons from dt embryos revealed that alpha-internexin was aggregated in the proximal region of axons and juxtanuclear region of the cytoplasma, yet the other intermediate filament proteins were widely distributed in all processes. The active caspase-3 activity was observed in the dt neuron with massive accumulation of alpha-internexin. From our observations, we suggest that the interaction between BPAG1 and alpha-internexin may be one of the key factors involved in neuronal degeneration, and abnormal accumulation of alpha-internexin may impair the axonal transport and subsequently turns on the cascade of neuronal apoptosis in dt mice.
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuang-Wen
authors.initials: KW
authors.lastname: Tseng
authors.forename: Kuo-Shyan
authors.initials: KS
authors.lastname: Lu
authors.forename: Chung-Liang
authors.initials: CL
authors.lastname: Chien
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001370:Axonal Transport / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D000071821:Dystonin; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D008818:Mice, Neurologic Mutants; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C095667:Dst protein, mouse; D000071821:Dystonin; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C046643:alpha-internexin; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases