General information

Mice:  C57BL/6

Conditional expression of the full-length human mutated (G2019S) LRRK2 protein was achieved through crossing of heterozygous knockin mice, expressing the tetracycline transactivatior (tTA) under the control of a Pitx3-IRES2 sequence, with mice expressing the mutated human LRRK2, HA tagged, under the control of the tetracycline operator.

Note: In this tet-off system, the animals express the transgene in absence of tetracycline or doxycycline treatment.

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:  Liu 2015

Transgene expression

  • Postnatal day 1: No expression of the transgene is detected.
  • 1 month: Expression of the human LRRK2G2019S protein seems restricted to nigral dopaminergic neurons (6 fold increase compared to control mice), no staining can be seen in the striatum.


  • 18 months: The density of TH- positive axons is significantly reduced in the striatum of transgenic animals
  • 20 months: No obvious neurodegeneration is observed in the SN or ventral tegmental area.

Dopamine Homeostasis

  • 1 months: A slight decrease in striatal DA metabolite DOPAC contents
  • 12 months: A slight decrease in striatal DA content.


  • Not reported

Motor Behaviours

  • 2, 6, 12 and 18 months: No differences can be observed in these transgenic animals compared to control littermates (open field, rotator and gait analysis).

Response to dopaminergic treatment

  • Not reported

Non-motor Behaviours

  • Not reported


  • 1 and 12 months: A significant decrease in single electrical pulse-evoked DA release can be measured in striatal brain slices at 12 months but not at 1 month of age.


  • 20 months: No sign of astrocytosis or microgliosis is observed in the midbrain the transgenic mice.

Updated 16/05/2018