DDD mice, a novel acute mouse model of Parkinson's disease.
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.
Sotnikova
Tatyana D
TD
Department of Cell Biology and Center for Models of Human Disease, IGSP, Duke University Medical Center, Durham, North Carolina 27710, USA.
Caron
Marc G
MG
Gainetdinov
Raul R
RR
D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004298:Dopamine / Q000172:deficiency; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology; D010641:Phenotype
D000978:Antiparkinson Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D004298:Dopamine