A Possible Cellular Mechanism of Neuronal Loss in the Dorsal Root Ganglia of Dystonia musculorum (dt) Mice

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...

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Bibliographic Details
Published in:Journal of neuropathology and experimental neurology 2006-04, Vol.65 (4), p.336-347
Main Authors: Tseng, Kuang-Wen, Lu, Kuo-Shyan, Chien, Chung-Liang
Format: Article
Language:English
Subjects:
Alcoholism and acute alcohol poisoning
Animals
Apoptosis - physiology
Axonal Transport - physiology
Biological and medical sciences
Carrier Proteins - genetics
Carrier Proteins - metabolism
Caspase 3
Caspases - metabolism
Cells, Cultured
Cytoskeletal Proteins - genetics
Cytoskeletal Proteins - metabolism
Dystonin
Errors of metabolism
Ganglia, Spinal - metabolism
Ganglia, Spinal - pathology
Immunohistochemistry
In Situ Hybridization
In Situ Nick-End Labeling
Intermediate Filament Proteins - metabolism
Lipids (lysosomal enzyme disorders, storage diseases)
Medical sciences
Metabolic diseases
Mice
Mice, Neurologic Mutants
Microscopy, Electron, Transmission
Mutation
Nerve Degeneration - genetics
Nerve Degeneration - pathology
Nerve Degeneration - physiopathology
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neurology
Neurons - metabolism
Neurons - pathology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
Toxicology
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Summary: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 α-internexin was absent in the DRG neurons in adult dt mice. To study the relationship between the absence of α-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 α-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 α-internexin. From our observations, we suggest that the interaction between BPAG1 and α-internexin may be one of the key factors involved in neuronal degeneration, and abnormal accumulation of α-internexin may impair the axonal transport and subsequently turns on the cascade of neuronal apoptosis in dt mice.
ISSN:0022-3069
1554-6578
DOI:10.1097/01.jnen.0000218448.39944.f1