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Neurology supplements are not peer-reviewed. Information contained in Neurology supplements represent the opinions of the authors and are not endorsed by nor do they reflect the views of the American Academy of Neurology, Editor-in-Chief, or Associate Editors of Neurology.

DDD mice, a novel acute mouse model of Parkinson’s disease

From the Department of Cell Biology and Center for Models of Human Disease, IGSP, Duke University Medical Center, Durham, North Carolina.

Address correspondence and reprint requests to Dr. Marc G. Caron, Box 3287, Duke University Medical Center, Durham, NC 27710; e-mail: caron002{at}mc.duke.edu

We describe the development of a novel animal model of acute severe dopamine (DA) deficiency by using genetically altered mice lacking the DA transporter (DAT-KO mice). In the absence of a DAT-mediated recycling mechanism in these mice, striatal DA concentrations become entirely dependent on its de novo synthesis, and acute pharmacologic inhibition of tyrosine hydroxylase induces transient (up to 16 hours) elimination of brain DA. Dopamine-deficient DAT-KO mice (DDD mice) demonstrate a striking behavioral phenotype manifested as severe akinesia, rigidity, tremor, and ptosis. We propose that DDD mice represent a novel acute model of severe DA deficiency that might be used to identify compounds with potential therapeutic use for the treatment of Parkinson’s disease (PD). This model is particularly promising as a tool for evaluating the efficacy of compounds that may induce movement independently of DA. The advantages and limitations of DDD mice in comparison to other rodent PD models are discussed.

Supported in part by grants from the National Institutes of Health NS-19576, MH-40159 and the Michael J. Fox Foundation for Parkinson’s Research.

Publication of this supplement was supported by a grant from Newron Pharmaceuticals.

Disclosure: The authors report no conflicts of interest.

Neurology supplements are not peer-reviewed. Information contained in Neurology supplements represents the opinions of the authors and is not endorsed by nor does it reflect the views of the American Academy of Neurology, Editorial Board, Editor-in-Chief, or Associate Editors of Neurology.