General Information

Rat: Sprague-Dawley

These rats express the tetracycline-controlled transactivator under a constitutive promoter (CAG-tTA) and the human mutant (G2019S) LRRK2 gene tagged with HA and under the control of a tetracycline-responsive element (TRE)-fused mini-cytomegalovirus promoter. In this model, the human mutant G2019S LRRK2 gene is expressed in the absence of tetracycline or its derivatives (e.g. Doxycycline (Dox)).

Endogenous rat 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.

Mutated gene: LRRK2

References: Zhou 2011

Transgene expression

  • Transgene expression is confirmed in the brainstem.


  • 18 months: No loss of TH positive neurons in SN or locus coeruleus.

Dopamine Homeostasis

  • 18 months: No significant changes in striatal levels of DA, DOPAC or HVA. However, the increase in striatal DA levels induced by treatments witj amphetamine and the dopamine-reuptake inhibitor nomifensine is smaller in animals temporally expressing LRRK2G2019S (from 5 months of age) than the peak observed in non-transgenic mice or in animals constitutively expressing LRRK2G2019S.


  • No alpha-synuclein, ubiquitin, or phosphorylated tau positive inclusion is observed in this model.

Motor Behaviours

  • 6-14 months: No difference is observed in open-field activity (distance travelled or number of stereotypic events) between transgenic animals (constitutively or temporally expressing LRRK2G2019S) and wild-type animals.
  • 18 months: There is no difference between non-transgenic animals and rats expressing the LRRK2G2019S transgene constitutively in the open field. However, rats temporally expressing the LRRK2G2019S transgene (from 5 months of age) show an increase in spontaneous activity when placed in the open-field. Yet, the increase in activity induced by amphetamine and nomifensine treatments is limited compared to the one observed in non-transgenic animals or LRRK2G2019S constitutively expressing animals.

Response to dopaminergic treatment

  • Not reported.

Non-motor Behaviours

  • Not reported.


  • Not reported.


  • Not reported.