Drosophila parkinmutants have decreased mass and cell size and increased sensitivity to oxygen radical stress

Author:

Pesah Yakov1,Pham Tuan2,Burgess Heather2,Middlebrooks Brooke2,Verstreken Patrik3,Zhou Yi4,Harding Mark2,Bellen Hugo1354,Mardon Graeme12354

Affiliation:

1. Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030,USA

2. Department of Pathology, Baylor College of Medicine, Houston, TX 77030,USA

3. Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA

4. Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA

5. Department of Molecular and Human Genetics, Baylor College of Medicine,Houston, TX 77030, USA

Abstract

Mutations in the gene parkin in humans (PARK2) are responsible for a large number of familial cases of autosomal-recessive Parkinson disease. We have isolated a Drosophila homolog of human PARK2 and characterized its expression and null phenotype. parkin null flies have 30% lower mass than wild-type controls which is in part accounted for by a reduced cell size and number. In addition, these flies are infertile, show significantly reduced longevity, and are unable to jump or fly. Rearing mutants on paraquat, which generates toxic free radicals in vivo, causes a further reduction in longevity. Furthermore, loss of parkin results in progressive degeneration of most indirect flight muscle (IFM) groups soon after eclosion, accompanied by apoptosis. However, parkin mutants have normal neuromuscular junction recordings during the third larval instar stage, suggesting that larval musculature is intact and that parkinis required only in pupal and adult muscle. parkin flies do not show an age-dependent dopaminergic neuron loss in the brain, even after aging adults for 3 weeks. Nevertheless, degeneration of IFMs demonstrates the importance of parkin in maintaining specific cell groups, perhaps those with a high-energy demand and the concomitant production of high levels of free radicals. parkin mutants will be a valuable model for future analysis of the mechanisms of cell and tissue degeneration.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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