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: PMID Zhou-2011-21698001
Transgene expression
Transgene expression is confirmed in the brainstem.
Neurodegeneration
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 with 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.
Inclusions
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 constitutively expressing the LRRK2G2019S transgene 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.
Electrophysiology
Not reported.
Neuroinflammation
Not reported.