General Information

Rat: Wistar

 The full-length human mutant (T240R) Parkin gene is expressed unilaterally in the SN using Adeno-Associated virus 2/8 (AAV2/8).

Endogenous Parkin: Yes

Corresponding human genotype:  The T240R mutation is one of the first point mutations identified in the Parkin gene.

Targeted gene: Parkin

References: Van Rompuy 2014

Viral injection

Injection coordinates: Right SN -. one deposition site: AP −3.1 mm, ML −1.2 mm, DV −4.0 mm.

Volume of injection and viral titer: two microliters of AAV2/8 vector are injected at a concentration of 2 × 10¹¹ GC/ml

Transgene expression

4 and 12 days then 1, 2, 4 and 8 months post-injection: The transgene is expressed in neurons of the SN and ventral tegmental are (VTA); very little expression is detected in astrocytes and microglia cells. The volume of the transduced area is maximal after 12 days and gradually decreases thereafter.

Neurodegeneration

1, 2, 4 and 8 months post-injection: Loss of TH- positive neurons in the SN is visible 2 months post-injection and increases over time. Similar degeneration is observed in VMAT2 expression (immunostaining). The loss of TH positive projections is maximal at 4 months; a partial recovery can be observed 8 months post-injection.

Dopamine Homeostasis

Not reported

Inclusions

Not reported

Motor Behaviours

4 days then 1, 2, 4 and 8 months post-injection: No significant changes is observed in the cylinder test.

Response to dopaminergic treatment

Not reported

Non-motor Behaviours

Not reported

Electrophysiology

Not reported

Neuroinflammation

4 days and 1 month: An increased inflammation is observed mostly along the needle track (CD68 staining) in the rats expressing the human T240R gene after one month.