Rat: Long Evans Hooded rats
A 5bp deletion in the exon 4 of the Parkin gene, leads to a frame-shift and introduction of a premature stop codon in exon 5.
The animals described here are homozygous knockout rats.
Endogenous Parkin: No
Corresponding human genotype: In humans the deletion, duplication or triplication of exons 2 was found to be associated with Parkinson’s disease.
Targeted gene: Parkin
- Absence of Parkin expression confirmed by western blot.
- 4, 6 and 8 months: No significant degeneration can be observed in the SN of KO rats.
- 2, 4, 6 and 8 months: No changes in levels of serotonin, DA and DA metabolites (DOPAC and HVA) are observed in KO rats compared WT animals.
Interestingly, a significant reduction of MAO-A and MOA-B activity is observed in the striatum. No changes are detected in MAO-A and MAO-B protein levels (2 months).
A reduction in the expression of presynaptic DA receptor 2 (D2) is detected in the striatum.
- 4, 6 and 8 months: No alpha-synuclein positive inclusions are observed in the brain of KO rats.
- 4, 6 and 8 months: No gait or motor impairment (rotarod, gait analysis) are observed in KO rats.
Response to dopaminergic treatment
- 2 months: A decrease in the locomotor response to amphetamine injection (2mg/kg) is observed
- 4, 6 and 8 months: No differences are observed between KO and wild type rats (approach, startle, pupil, touch or tail pinch responses)
- Not reported
- Not reported