Functional conservation of human Spastin in a Drosophila model of autosomal dominant-hereditary spastic paraplegia.

ABSTRACT: Mutations in spastin are the most frequent cause of the neurodegenerative disease autosomal dominant-hereditary spastic paraplegia (AD-HSP). Drosophila melanogaster lacking spastin exhibit striking behavioral similarities to human patients suffering from AD-HSP, suggesting conservation of Spastin function between the species. Consistent with this, we show that exogenous expression of wild-type Drosophila or human spastin rescues behavioral and cellular defects in spastin null flies equivalently. This enabled us to generate genetically representative models of AD-HSP, which arises from dominant mutations in spastin rather than a complete loss of the gene. Flies co-expressing one copy of wild-type human spastin and one encoding the K388R catalytic domain mutation in the fly spastin null back

SUBMITTER: Du F 

PROVIDER: S-EPMC2860889 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature