Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease

M. Meulener, A.J. Whitworth, C.E. Armstrong-Gold, P. Rizzu-Heutink, P. Heutink, P.D. Wes, L.J. Pallanck, N.M. Bonini

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder that displays both sporadic and inherited forms [1]. Exposure to several common environmental toxins acting through oxidative stress has been shown to be associated with PD [2]. One recently identified inherited PD gene, DJ-1, may have a role in protection from oxidative stress [3-10], thus potentially linking a genetic cause with critical environmental risk factors. To develop an animal model that would allow integrative study of genetic and environmental influences, we have generated Drosophila lacking DJ-1 function. Fly DJ-1 homologs exhibit differential expression: DJ-1β is ubiquitous, while DJ-1α is predominantly expressed in the male germline. DJ-1α and DJ-1β double knockout flies are viable, fertile, and have a normal lifespan; however, they display a striking selective sensitivity to those environmental agents, including paraquat and rotenone, linked to PD in humans. This sensitivity results primarily from loss of DJ-1β protein, which also becomes modified upon oxidative stress. These studies demonstrate that fly DJ-1 activity is selectively involved in protection from environmental oxidative insult in vivo and that the DJ-1β protein is biochemically responsive to oxidative stress. Study of these flies will provide insight into the critical interplay of genetics and environment in PD. ©2005 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)1572-1577
JournalCurrent Biology
Volume15
Issue number17
Early online date6 Sep 2005
DOIs
Publication statusPublished - 2005

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