General Information

Mice: C57BL/6J

These mice express the G2019S mutation in the endogenous mLRRK2 gene. The knockin mutation was generated in codon 2019 thanks to a two base mutagenesis, changing the triplet GGG to AGC or to TCG in exon 41 of the mouse LRRK2 gene. Animals described below are homozygous for the mutation.

Endogenous LRRK2: mutated G2019S

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: Herzig 2011-; Longo 2014, Beccano-Kelly 2014, Yue 2015, Matikainen-Ankney 2016, Volta 2017

Transgene expression

  • 3, 12 and 20 months: The levels of mutated LKKR2 protein present in hemi-brain or striatal lysates are the same in mice homozygous and heterozygous and are comparable to levels observed in wild-type animals.


  • Up to 22 months: Striatal level of TH is similar to that of wild type animals. No differences in the number of TH-positive cells counted in the SN and no gross changes (hematoxylin eosin, neurofilament or DARPP-32 staining) are observed in the brain of transgenic animals when compared to control littermates.

Dopamine Homeostasis

  • 6, 12 and 18 months: Freely moving animals, bearing the G2019S mutation, present lower levels of striatal DA than wild-type mice (awake microdialysis, only at 12 months), although no significant difference is observed ex vivo (post-mortem HPLC).
    The levels of DA metabolites (DOPAC or HVA) decrease with age but remain similar in transgenic and control animals.
    Amphetamine-induced DA release might be altered in older animals (12 months) but DA, DOPAC and HVA levels are not significantly different.
  • 22 months: Quantifications of striatal TH and DA transporters do not differ between transgenic animals and control littermates.


  • Up to 18 months: No difference in alpha-synuclein staining is visible in the brain of transgenic mice. However, phosphorylated-tau positive puncta are observed in some old (over 18 months) transgenic mice but not in paired littermate control mice.

Motor Behaviours

  • 6 months: No differences are observed in the open field, except a slight tendency for the G2019S animals to travel longer distances than the wild-type animals (only in one study). Motor testing for gait dynamics shows no differences between homozygous and wild type animals. Transgenic animals seem to be more active than the control mice during the bar, drag and cylinder tests and performed better on the rotarod (only significant in one study).
  • 12 months: Very limited changes are observed and only within the first 300s spent in the open field: transgenic animals make more entries and spend more time in the centre zone, they also freeze more frequently and for longer periods than their non-transgenic littermates. Motor testing for gait dynamics and rotarod show no differences between transgenic and wild type animals.
  • 15 months: transgenic animals are significantly more active in the open field and show better performances on the bar and drag test compared to the control littermates.

Response to dopaminergic treatment

  • Not reported

Non-motor Behaviours

  • 6 and 12 months: No differences can be observed between transgenic and non-transgenic animals on any of the following tests: novel object recognition, elevated plus maze, light dark exploration or conditioned fear or Morris water maze suggesting the absence of memory impairment or anxiety.


  • 21 days: Changes in the neuronal activity (action potential-dependent synaptic activity) is observed in the medium spiny neurons of transgenic mice.
  • 1-3 months: Increased in glutamate and DA transmission are observed in transgenic animals compared to control littermates (whole-cell patch-clamp recording of striatal medium spiny neurons, only at this young age).
  • 6 and 12 months: The intrinsic membrane properties of striatal medium spiny neurons and glutamate release ability are not altered in transgenic animals (ex-vivo whole-cell patch-clamp: membrane capacitance, membrane resistance, and decay time constants). However, transgenic mice show an increased in glutamatergic release frequency.


  • Up to 20 months: No visible differences are observed in glia (Iba-1) or astrocyte staining (GFAP).

Updated 16/05/2018