DrosophilaOverexpressing Parkin R275W Mutant Exhibits Dopaminergic Neuron Degeneration and Mitochondrial Abnormalities

• DOI: 10.1523/jneurosci.0218-07.2007
• Publication Date: 2007-08-08T17:23:23Z
• Authors: Cheng Wang; Ruifeng Lu; Xuezhi Ouyang; Michelle W. L. Ho; William Chia; Fengwei Yu; Kah-Leong Lim
• Keywords: PINK1

Mutations in the parkin gene are a predominant cause of familial parkinsonism. Although initially described as recessive disorder, emerging evidence suggest that single mutations alone may confer increased susceptibility to Parkinson's disease. To better understand effects vivo , we generated transgenic Drosophila overexpressing two human missense mutants, R275W and G328E. Transgenic flies overexpress R275W, but not wild-type or G328E, display an age-dependent degeneration specific dopaminergic neuronal clusters concomitant locomotor deficits accelerate with age response rotenone treatment. Furthermore, mutant also exhibit prominent mitochondrial abnormalities their flight muscles. Interestingly, these defects caused by expression highly similar those triggered loss endogenous null flies. Together, our results provide first demonstrating mediates pathogenic outcomes interesting possibility select directly exert neurotoxicity .