Delta FY Mutation in Human Torsina Induces Locomotor Disability and Abberant Synaptic Structures in Drosophila

We investigate the molecular and cellular etiologies that underlie the deletion of the six amino acid residues (Delta F323-Y328; Delta FY) in human torsin A (HtorA). The most common and severe mutation involved with early-onset torsion dystonia is a glutamic acid deletion (Delta E 302/303; Delta E) in HtorA which induces protein aggregates in neurons and cells. Even though Delta FY HtorA forms no protein clusters, flies expressing Delta FY HtorA in neurons or muscles manifested a similar but delayed onset of adult locomotor disability compared with flies expressing Delta E in HtorA. In addition, flies expressing Delta FY HtorA had fewer aberrant ultrastructures at synapses compared with flies expressing Delta E HtorA. Taken together, the Delta FY mutation in HtorA may be responsible for behavioral and anatomical aberrations in Drosophila.