General Information

Rat: Sprague Dawley 

Expression of the human full-length mutant (R1441C) LRRK2 N-terminally fused to a YPet in rats using the bacterial artificial chromosome (BAC).

Endogenous rat LRRK2: yes

Corresponding human genotype: R1441C is an autosomal dominant missense mutation in the LRRK2 gene.

Mutated gene: LRRK2

References: Sloan 2016

Transgene expression

  • 3 months: Expression of mutant LRRK2 is observed in striatal cholinergic interneurons. A low expression is also observed in SN TH-positive neurons. Expression level of the mutant protein is 4-5 times that of endogenous rat LRRK2. Expression levels at later time are not reported.


  • 18-22 months: No loss of TH-positive neurons or change in neuronal morphology is observed in the SN

Dopamine Homeostasis

  • 18-21 months: No difference in striatal dopamine content


  • 18-21 months: No inclusions and no increase in alpha-synuclein reactivity are observed in the SN

Motor Behaviours

  • 3-6 months: No motor impairments are observed.
  • 18-21 months: impaired performances are observed on the accelerating rotarod. No gait disturbance is detected

Response to dopaminergic treatment

  • 18-21 months: Significant response to L-DOPA

Non-motor Behaviours

  • Short-term memory (T-maze): age-dependent impairment in spontaneous alternation performances are observed at 18-21 months but not at 3-6 months
  • Gastrointestinal function: no alterations are observed at any time


  • 6-12 months: No changes in electrical stimulation-evoked DA release are observed in the dorsal striatum. DA content and reuptake rate are not altered.
  • 18-22 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 in the firing rates of SN DA neurons is observed, however, the frequency of bursts and the percentage of spikes fired as bursts are reduced in transgenic animals.


  • 18-21 months: no changes in the number of glial cells (microglia) are observed compared to non-transgenic littermates. Earlier time points are not reported.