Parkin-KO-Rat

General Information

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

 References: Dave 2014;  Gemechu 2018

Transgene expression

• Absence of Parkin expression confirmed by western blot.

Neurodegeneration

• 4, 6 and 8 months: No significant degeneration can be observed in the SN of KO rats.

Dopamine Homeostasis

•  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.

Inclusions

• 4, 6 and 8 months: No alpha-synuclein positive inclusions are observed in the brain of KO rats.

Motor Behaviours

• 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

Non-motor Behaviours

• 4, 6 and 8 months:  No differences are observed between KO and wild type rats (approach, startle, pupil, touch or tail pinch responses)

Electrophysiology

• Not reported

Neuroinflammation

• Not reported