General Information

Mice: C57BL/6J

Expression of the full-length mouse wild type LRRK2 protein using the bacterial artificial chromosome (BAC).

Endogenous LRRK2: yes

Corresponding human genotype: LRRK2 is the greatest known genetic contributor to Parkinson’s disease.

Targeted gene: LRRK2

References: Li 2010, Sweet 2015

Transgene expression

  • 6 months: Protein expression is about 6 fold higher than that of the endogenous LRRK2 in the striatum of transgenic animals.

Neurodegeneration

  • Up to 18 months: No differences is observed in the number of TH-positive cells in the SN or in the density of TH fibres measured in the striatum.

Dopamine Homeostasis

  • 6 and 12 months: No differences in the level of DA and HVA are observed in the striatum of these animals (compared to control mice).
  • 10 months: no differences are observed in striatal TH protein levels, enzymatic activity, or phosphorylation state when compared to control mice. Similarly VMAT2, DAT, or D2 receptor levels are comparable to wild type animals.

Inclusions

  • Up to 18 months: No alpha-synuclein and/or ubiquitin inclusions are visible.

Motor Behaviours

  • 6 and 12 months: The overall activity of the animals is increased: more rearing events (at both time points), longer distances travelled and longer periods of activity (only at 12 months) in the open field than the littermate control mice or LRRK2G2019S transgenic animals (add link to page). The animals also make more mistakes on the challenge beam (slips and slips/step) than the control or LRRK2G2019S transgenic mice.

Response to dopaminergic treatment

  • Not reported

 Non-motor Behaviours

  • Not reported

Electrophysiology

  • 12 months: An increase in electrical stimulation-evoked DA release is observed in LRRK2 transgenic animals compared to paired littermate control mice (fast-scan cyclic voltammetry). However, the maximum uptake rate of DA is not altered.
  • 3-5 months and 8-12 months: No electrophysiological changes can be observed in the dorsal hippocampus of transgenic animals. Basal synaptic efficiency, presynaptic function and long-term depression (LTD) remain unaltered.

Neuroinflammation

  • Not reported