Behavioral and neurotransmitter abnormalities in mice deficient for Parkin, DJ-1 and superoxide dismutase

PLoS One. 2013 Dec 26;8(12):e84894. doi: 10.1371/journal.pone.0084894. eCollection 2013.


Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by loss of neurons in the substantia nigra that project to the striatum and release dopamine. The cause of PD remains uncertain, however, evidence implicates mitochondrial dysfunction and oxidative stress. Although most cases of PD are sporadic, 5-10% of cases are caused by inherited mutations. Loss-of-function mutations in Parkin and DJ-1 were the first to be linked to recessively inherited Parkinsonism. Surprisingly, mice bearing similar loss-of-function mutations in Parkin and DJ-1 do not show age-dependent loss of nigral dopaminergic neurons or depletion of dopamine in the striatum. Although the normal cellular functions of Parkin and DJ-1 are not fully understood, we hypothesized that loss-of-function mutations in Parkin and DJ-1 render cells more sensitive to mitochondrial dysfunction and oxidative stress. To test this hypothesis, we crossed mice deficient for Parkin and DJ-1 with mice deficient for the mitochondrial antioxidant protein Mn-superoxide dismutase (SOD2) or the cytosolic antioxidant protein Cu-Zn-superoxide dismutase (SOD1). Aged Parkin -/-) DJ-1(-/-) and Mn-superoxide dismutase triple deficient mice have enhanced performance on the rotorod behavior test. Cu/Zn-superoxide dismutase triple deficient mice have elevated levels of dopamine in the striatum in the absence of nigral cell loss. Our studies demonstrate that on a Parkin/DJ-1 null background, mice that are also deficient for major antioxidant proteins do not have progressive loss of dopaminergic neurons but have behavioral and striatal dopamine abnormalities.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal*
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Crosses, Genetic
  • Dopamine / genetics
  • Dopamine / metabolism*
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Mice
  • Mice, Knockout
  • Oncogene Proteins / deficiency*
  • Oxidative Stress / genetics
  • Peroxiredoxins
  • Protein Deglycase DJ-1
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Superoxide Dismutase / deficiency*
  • Superoxide Dismutase-1
  • Ubiquitin-Protein Ligases / deficiency*


  • Oncogene Proteins
  • Peroxiredoxins
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • superoxide dismutase 2
  • Ubiquitin-Protein Ligases
  • parkin protein
  • PARK7 protein, mouse
  • Protein Deglycase DJ-1
  • Dopamine