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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Sotnikova, TD; Caron, MG; Gainetdinov, RR

Published Date

  • October 10, 2006

Published In

Volume / Issue

  • 67 / 7 Suppl 2

Start / End Page

  • S12 - S17

PubMed ID

  • 17030735

Pubmed Central ID

  • 17030735

Electronic International Standard Serial Number (EISSN)

  • 1526-632X

Digital Object Identifier (DOI)

  • 10.1212/wnl.67.7_suppl_2.s12


  • eng

Conference Location

  • United States