Recombinant Adeno-Associated Virus-mediated rescue of function in a mouse model of Dopamine Transporter Deficiency Syndrome

Sci Rep. 2017 Apr 18:7:46280. doi: 10.1038/srep46280.


Dopamine Transporter Deficiency Syndrome (DTDS) is a rare autosomal recessive disorder caused by loss-of-function mutations in dopamine transporter (DAT) gene, leading to severe neurological disabilities in children and adults. DAT-Knockout (DAT-KO) mouse is currently the best animal model for this syndrome, displaying functional hyperdopaminergia and neurodegenerative phenotype leading to premature death in ~36% of the population. We used DAT-KO mouse as model for DTDS to explore the potential utility of a novel combinatorial adeno-associated viral (AAV) gene therapy by expressing DAT selectively in DA neurons and terminals, resulting in the rescue of aberrant striatal DA dynamics, reversal of characteristic phenotypic and behavioral abnormalities, and prevention of premature death. These data indicate the efficacy of a new combinatorial gene therapy aimed at rescuing DA function and related phenotype in a mouse model that best approximates DAT deficiency found in DTDS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Corpus Striatum / metabolism
  • Dependovirus / genetics*
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins / deficiency*
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Gene Expression
  • Gene Order
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics*
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Neurons / metabolism
  • Phenotype
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Syndrome
  • Transduction, Genetic*
  • Treatment Outcome


  • Dopamine Plasma Membrane Transport Proteins
  • Slc6a3 protein, mouse
  • Dopamine