The full-length human wild type LRRK2 was introduced in Sprague-Dawley rats using a bacterial artificial chromosome (BAC).
Endogenous rat LRRK2 : yes
Corresponding human genotype: LRRK2 is the greatest known genetic contributor to Parkinson’s disease.
Mutated gene: LRRK2
References: Sloan 2016
- The transgene is expressed throughout the brain at different levels (4-5 fold higher than the endogenous LRRK2). The human LRRK2 protein is present at low level in the SNand high level in the hippocampus.
- Not reported
- Not reported
- 18-21 months: No inclusions positive for alpha-synuclein, phosphorylated Tau (pSer202/Thr205: AT8) or ubiquitin observe in the SNpc.
- 3-6 and 18-21 months: Motor performances of the transgenic animals appear normal on the accelerating rotarod, grip test and drag test.
Response to dopaminergic treatment
- Not applicable in the absence of motor impairment.
- 3-6 and 18-21 months: Performances of the transgenic animals on the spontaneous alternation test appear normal.
- 6 and 12 months: no changes in electrical stimulation-evoked DA are observed in the dorsal or ventral striatum. Dopamine content and reuptake rate are not altered.
- 18-21 months: a decrease in electrical stimulation-evoked DA release is observed in the dorsal striatum. DA content and reuptake rate are not altered suggesting a reduced ability to release DA. No difference is observed in the firing rates of SN dopamine neurons.
- 18-21 months: no changes in the number of glial cells (microglia) are observed compared to non-transgenic littermates.