A 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, and a defective bullous pemphigoid antigen 1 (BPAG1) gene is responsible for this mutation. In 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 by different approaches. We found that not only BPAG1 but also internexin was absent in the DRG neurons in adult dt mice. To study the relationship between the absence of 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 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 internexin. From our observations, we suggest that the interaction between BPAG1 and internexin may be one of the key factors involved in neuronal degeneration, and abnormal accumulation of internexin may impair the axonal transport and subsequently turns on the cascade of neuronal apoptosis in dt mice.