biostudies-literatureDu FNINDS NIH HHS1883-96https://www.ebi.ac.uk/biostudies/studies/S-EPMC2860889biostudies-literatureUnknown19(10)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 backHuman molecular geneticsFunctional conservation of human Spastin in a Drosophila model of autosomal dominant-hereditary spastic paraplegia.PMC2860889NS063896Ozdowski EFDu FMarchuk DASherwood NTKotowski IKfalseFunctional conservation of human Spastin in a Drosophila model of autosomal dominant-hereditary spastic paraplegia.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 back2010-01-01T00:00:00Z2010 May2025-04-22T05:11:23.312Z2019-03-27T00:30:24ZS-EPMC28608892015434210.1093/hmg/ddq064