General Information

Mouse: B6/129; C57BL6/J

Mice in which exon 2, containing the start codon, of the DJ-1 gene was deleted leading to the absence of DJ-1 protein in homozygous DJ-1-/- mice. Reproductive functions are not affected by the loss of DJ-1 expression.

A reduction in body weight is observed at 1 year in CB54BL6/J mice

Endogenous DJ-1: No

Corresponding human genotype: Autosomal recessive genetic deletion in the DJ-1 gene causing a loss-of-function of the protein and leading to early-onset Parkinson’s disease (PARK7).

Mutated gene: DJ-1

References: Goldberg 2005; Yamaguchi 2007; Chandra 2007; Bonilha 2015; Bonilha 2017 

Neurodegeneration

B6/129

  • Up to 27 months: No apparent changes in the number TH-positive neurons and terminals are observed (measures performed at 3, 12 and 24-27 months). Interestingly, no increase in the sensitivity to paraquat treatment is observed at 3 months.
    No changes are detected in noradrenergic neurons in the LC

C57BL6/J

  • 13, 22 and 28 months: No apparent changes in the number of TH-positive neurons in the SN and LC is observed
  • 3 and 6 months: reduced number of TH-positive neurons are observed in the retinas

Dopamine Homeostasis

B6/129

  • Up to 27 months: no changes in striatal levels of dopamine and dopamine metabolites are detected (measured at 3 months and 24-27 months)

C57BL6/J

  • 6 months: normal differences in extracellular DA concentration and DA uptake are observed in the striatum. No differences in evoked DA release is detected. No changes in expression of D2 autoreceptor activity is measured.

Inclusions

B6/129

  • Up to 27 months: No inclusions are observed in the SN/striatum(evaluated at 3, 12 and 24-27 months) or noradrenergic neurons in the LC (24-27 months).

C57BL6/J

  • Not reported

Motor Behaviours

B6/129

  • Up to 25 months: hypo-activity in the open field test is observed.
    A reduction in the horizontal activity test with fewer stereotyped behavior is detected.
    No differences are observed in the rotarod test as well as in the acoustic startle reflex paradigm.

C57BL6/J

  • 2 months: changes in stride uniformity and hind base placement are observed. No changes in stride lengths.
  • 5 and 14 months: reduced spontaneous locomotor activity suggesting hypokinisia is observed compared to wt mice (not present at 2 and 23 months).
  • 16 months: reduced grip strength in forelimbs is observed (deficit absent before that age). Enhanced motor learning is detected (accelerating rotarod)
  • 23 months: changes in stride uniformity, hind base placement and stride lengths are observed

Response to dopaminergic treatment

B6/129

  • 3 months: treatment with quinpirole, a D2 receptor agonist, significantly supressed locomotor activity to a higher degree in KO animals compared to wild type.

C57BL6/J

  • 24 months: L-DOPA treatment did not rescue the stride deficit in KO mice.

Non motor Behaviours

B6/129

  • Not reported

C57BL6/J

  • 2, 5, 14 and 23 months: no anxiety deficits (elevated plus maze) are detected.
  • 3 and 6 months: accelerated retinal abnormalities with aging

Electrophysiology

B6/129

  • 3 months: a marked decrease in evoked dopamine overflow is observed. Experiment in the presence of a Dopamine transporter blocker that blocks dopamine reuptake, nomifensine, indicates that reduced dopamine overflow is due to increase in dopamine reuptake.

C57BL6/J

  • Not reported

Neuroinflammation

B6/129

  • 24-27 months: No sign of GFAP activation is observed in the SN or the striatum

C57BL6/J

  • Not reported

Updated 25/04/2018