General Information

Rat: Long Evans Hooded

A 9bp deletion in the exon 5 of the DJ-1 gene, leads to a frame-shift and introduction of a premature stop codon in exon 6.

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:  Dave 2014, Yang 2018; Alzforum

Transgene expression

• The 9bp deletion destabilises the mRNA; no DJ-1 protein expression is observed in homozygous animals.

Loss of dopaminergic neurons

• 6 and 8 months: A significant reduction in the number TH-positive neurons in the SN and the LC. No changes are observed in the VTA and in TH-positive terminals in the striatum.

Dopamine Homeostasis

• 8 months: A significant increase (2-3 fold) in DA and DA metabolites is detected in the striatum. The overall turnover rate is not different between KO and WT animals.

Inclusions

• 4, 6 and 8 months: No inclusions are observed

Motor Behaviours

• 2, 4, 6 and 8 months: Impaired gait (abnormal paw positioning) and motor features are observed.
  A progressive reduction in the speed of traversal in the tapered balance beam test is observed.
• 6 and 8 months: A reduction in the total distance travelled of the rearing capacity are observed in open field tests.
• 8 months: a subset of animals (60%) showed lack of hind-limb extensor strength and lack of overall muscle tone.

Response to dopaminergic treatment

• Not reported

Non motor Behaviours

• 2, 4, 6 and 8 months: No differences can be seen in numerous tests (approach, startle, pupil, touch or tail pinch responses) between KO and WT animals.
  A progressive reduction in sensorimotor function (ultrasonic vocalization, tongue motor performance) is observed

Electrophysiology

• Not reported

Neuroinflammation

• Not reported

Updated 25/04/2018