Dystonia musculorum (dt), is an inherited mouse neuropathy characterized by progressive motor disorders. Dystonin (Dst) is a causative gene for dt mice. Although degeneration of the peripheral nervous system (PNS) during early postnatal stage is well-recognized phenotype in dt mice, histological appearance in the central nervous system (CNS) responsible for motor disorders are still unclear. We generated a novel Dst gene trap mice, DstGt, in which actin binding domain-containing isoforms are disrupted. Homozygous mice showed typical dt phenotypes with progressive neurological symptoms. The gene trap allele encodes for a mutant Dst-LacZ fusion protein which is detected by X-gal staining with high sensitivity. We observed severe motor disorders in their limbs and twisted postures. Electorophysiological study showed abnormal co-contractions of agonist and antagonist muscle in DstGt homozygotes. In histological aspects, abnormal neurofilament immunoreactivity was found in both somatosensory pathway and motor-related medullary reticular nucleus which showed high Dst expression. These results raise the possibility that cell-autonomous primary CNS defects contribute to dt phenotype.