An intrinsic neuronal defect operates in dystonia musculorum: a study of dt/dt<==>+/+ chimeras.

In the mouse mutant dystonia musculorum (dt), peripheral and central sensory axons develop focal swellings and degenerate. To identify the primary cellular target of the mutation, we have analyzed the spinal cords of dt/dt<==>+/+ aggregation chimeras. In these chimeras, characteristic swellings appeared only on the axons of mutant genotype neurons; the axons of wild-type neurons, identified by their expression of a transgene-encoded human neurofilament protein, were normal. This direct correlation of genotype and phenotype indicates that the dt mutation acts via a mechanism intrinsic to affected neurons. In addition, we show here that the dt mutation leads to a disorder of neurofilament processing in which phosphorylated neurofilament epitopes accumulate inappropriately in neuronal perikarya.