Mice in which exon 3-5 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.
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: Kim, 2005;Sanchez, 2014; Rousseaux 2012; Zhou 2017
Loss of dopaminergic neurons
- 8-10 weeks: No apparent changes in the number TH-positive neurons and terminals are observed. An increased sensitivity to MPTP treatment is observed in the striatum and the SNc.(Kim; SAnchez)
- 2 months: unilateral loss of TH-positive neurons is observed in the SN and not in the VTA of in a subset of animals. No reduction of DA terminals is observed in the striatum (suggesting neurites sprouting) at this age
- 15 months: Unilateral reduction of TH-positive terminals is observed in the striatum (reduced sprouting) and in the LC
- 8-10 weeks: no changes in striatal levels of dopamine and dopamine metabolites are detected. An increased sensitivity to MPTP is observed with a more pronounced reduction of dopamine levels observed in DJ-1-/- mice compared to wild type
- 8 weeks: no differences in dopamine evoked overflow is observed using FSCV
- 3 and 12 months: No inclusions are observed
- 8 weeks, 2, 6 and 13 months: No statistically significant differences are observed in spontaneous locomotor activity as measured in the open field test (both horizontal and vertical movements). Similarly, no changes in the pole test are detected.
- 14-16 months: mild motor deficit is observed (grid and pole test)
- 8-10 weeks: Treatment with MPTP caused a more significant reduction in spontaneous locomotor activity in DJ-1-/- compared to wild type mice. Reduced activity is observed in DJ-1-/- mice compared to wild type following amphetamine challenge (2mg/kg).
- 10 months: motor deficits is observed (rotarod)
Response to dopaminergic treatment
- Not reported
Non motor Behaviours
- 8 weeks and 13 months: no differences in novel environment and somatosensory tests are detected
- 10 months: normal cognitive function (Morris water maze and exploratory activity)
- not reported
- 2 months: animals displaying unilateral loss of TH-positive neurons in the SN show clear activation of microglial cells in the affected side. No astroglial activation is observed.