The full-length human Parkin gene is expressed unilaterally in the SN of rats using Adeno-Associated virus 2/8 (AAV2/8).
Endogenous Parkin: Yes
Corresponding human genotype: Parkin was the first gene associated with autosomal recessive Parkinson’s disease (PD).
Targeted gene: Parkin
References: Van Rompuy 2014
Injection coordinates: Right SN -. one deposition site : AP − 5.3 mm, ML −2.0 mm rel and DV −7.2 mm surface.
Volume of injection and viral titer: three microliters of AAV2/8 vector is injected at a concentration of 2 × 1011 GC/ml
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.
4 and 12 days then 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. A similar loss of VMAT2 is observed (immunostaining). The loss of TH positive projections is maximal at 4 months and a partial recovery is observed 8 months post-injection.
4 days then 1, 2, 4 and 8 months post-injection: Transgenic animals exhibit a bias in the use of forelimb paws in the cylinder test at 4 months; a recovery is observed at 8 months.
Response to dopaminergic treatment
4 days and 1 month: An increased inflammation is observed mostly along the needle track (CD68 staining) in the rats expressing the human Parkin gene after a month,