General Information

Mice: C57BL/6

Conditional expression of the full-length human mutant (G2019S) LRRK2 mutant protein was achieved using a Ca2+/calmodulin-dependent protein kinase II alpha (CaM) promoter to control the expression of the tetracycline-transactivator (tTA).

Note: In this tet-off system, the animals express the transgene in absence of tetracycline or doxycycline treatment. Keeping the animals under treatment during development prevents transgene expression and prevents possible compensation mechanisms to take place.

Endogenous LRRK2: yes

Corresponding human genotype: The G2019S substitution in the LRRK2 gene is believed to be the most common mutation associated with Parkinson’s disease. It is located in the kinase domain of the protein.

Targeted gene: LRRK2

References: Lin-2009, Xiong 2007

Transgene expression

Note: Animals are kept under doxycycline treatment until the pups are weaned (at about 2months of age)

  • 2 months: The human mutated LRRK2G2019S transgene is expressed in the striatum (17 fold increased compared to endogenous mouse gene), ventral midbrain (4 fold) olfactory bulb (5 fold), cortex (15 fold) and hippocampus (9 fold) but not in the brainstem or cerebellum.


  • Up to 22 months: No obvious neurodegeneration in the SN. The density of tyrosine hydroxylase positive axons in the striatum of the LRRK2G2019S transgenic animals remained unaltered.

Dopamine Homeostasis

  • Not reported


  • Up to 15 and: No differences in the levels of alpha-synuclein or phosphorylated alpha-synuclein are observed in the brain of LRRK2G2019S transgenic mice up to 15 months compared to non-transgenic littermates.
  • 22 months: the amount of triton insoluble alpha-synuclein protein is significantly higher in the striatum, cortex, hippocampus and olfactory bulb of these transgenic mice.

Motor Behaviours

  • Up to 12 months: No differences is observed in transgenic animals compared to control littermates up to 12 months (open field, activity cage, pole and rotarod tests).
  • 12 to 22 months: The transgenic mice show an increased activity in the activity cage after 12 months but difficulties descending the pole at 22 months.

Response to dopaminergic treatment

  • Not reported

Non-motor Behaviours

  • Not reported


  • Not reported


  • Not reported