DYSTONIN EXPRESSION IN THE DEVELOPING NERVOUS-SYSTEM PREDOMINATES IN THE NEURONS THAT DEGENERATE IN DYSTONIA MUSCULORUM MUTANT MICE

Dystonia musculorum (dt) is an inherited neurodegenerative disorder in mice. The dt gene product, dystonin, contains the bullous pemphigoid antigen 1 coding region at its C-terminus and an actin binding domain at its N-terminus. We demonstrate that dystonin expression throughout mouse development predominates in neurons of the cranial and spinal se nsory ganglia. Those structures are the most severely affected in dyst onic mice which could explain their severe sensory ataxia. Since we sh ow expression in sensory neurons with small and large axoplasmic volum es, but degeneration is restricted primarily to the latter type, we su ggest that caliber and size of the axon is an important factor in the diseases process. Dystonin is also expressed in the extrapyramidal mot or system and in the cerebellum. Functional defects in these cell type s could account for the dystonic symptoms of df mice not explained by simple sensory denervation. We also detect dystonin expression in moto r neurons most of which are unaffected by the degenerative process in dt mice.