Reducinggene dosage induces dopaminergic neuronal loss and motor impairments inknockout mice.

Abstract

Mutations in thegene are associated with early onset Parkinsonism. Themouse, however, does not exhibit neurodegeneration or other Parkinson's disease (PD) phenotypes. Previously, we discovered that translation of Mcl-1, a pro-survival factor, is upregulated in themouse, suggesting a compensatory mechanism during development. Here we generated themouse and show that by reducinggene dosage by 50%, thegenotype is sensitized, conferring both dopaminergic neuron loss and motor impairments. We propose that this murine model could be a useful tool for dissecting PD etiology and developing treatment strategies against this neurodegenerative disease.