Abnormal cellular translocation of alpha-internexin in spinal motor neurons of Dystonia musculorum mice.

Dystonia musculorum (dt) is a mutant mouse with hereditary neuropathy where the dysfunction is mainly found in the dorsal root ganglia (DRG) neurons but not in the spinal motor neurons. However, the accumulation of intermediate filament (IF) proteins in the swelling axons of spinal motor neurons could be found in dt/dt mice. In order to understand the pathological role of neuronal IFs in the swelling axons of spinal motor neurons from dt/dt mice, we extensively examined the distribution of neuronal IF proteins. By immunofluorescence staining, our results indicated that alpha-internexin was a major component in the swelling axon and showed abnormal translocation in the nuclei of spinal motor neurons in dt/dt mice. This abnormal translocation of alpha-internexin in the nuclei of spinal motor neurons was also confirmed by Western blotting and immunoelectron microscopy. Instead of the 10-nm filamentous structure, a diffuse immunopositive pattern of alpha-internexin was observed in the nucleus of spinal motor neurons in dt/dt mutants. We further examined the cell death of spinal motor neurons by TUNEL assay, and no TUNEL-positive cells could be identified from spinal motor neurons in dt/dt mice. From these observations we suggest that abnormal accumulation of neuronal IFs in the swelling axons and abnormal translocation of alpha-internexin in the nuclei of the spinal motor neurons from dt/dt mice may not directly cause cell death of the spinal motor neurons.