General Information
Mice: FBV/N
Expression of the full-length human wild type LRRK2 protein, HA-tagged, under the control of a CMV enhancer (CMVE) and platelet-derived growth factor beta (PDGF).
Endogenous LRRK2: yes
Corresponding human genotype: LRRK2 is a major known genetic contributor to Parkinson’s disease.
Targeted gene: LRRK2
References: Ramonet 2011, Chen 2012, Weng 2016
Transgene expression
- 2-3 months: The human transgene is expressed 3-5 fold the level of the endogenous LRRK2. Human LRRK2 expression is observed throughout the brain of transgenic animals, however, no hwt LRRK2 mRNA is detectable in the midbrain.
- 10 months: Transgene is expressed in the SN in 70% of TH positive cells. Expression is also observed in the cortex and cerebellum.
Neurodegeneration
- Up to 16 months: No differences are observed in the number of tyrosine hydroxylase (TH) positive cells in the SN or TH positive fibres in the striatum of transgenic mice compared to control littermates. Similarly, neuronal cell degeneration can be observed in the cortex, hippocampus or striatum (NeuN staining).
Dopamine Homeostasis
- 16-17 months: Normal levels of DA and its metabolites (DOPAC, HVA) can be measured in the striatum, cortex and olfactory bulb of the transgenic animals.
Inclusions
- Up to 16 months: No abnormalities can be seen in α-synuclein, phosphorylated α-synuclein, ubiquitin or phosphorylated tau stained brain sections.
Motor Behaviours
- 12-20 months: No significant changes are observed during motor assessments (activity cages, downward pole test, up to 16 months or in the open field and cylinder, up to 20months).
Response to dopaminergic treatment
- 18 months: In absence of motor impairments, mice show, as expected, no significant effect of L-DOPA treatment.
Non-motor Behaviours
- Not reported
Electrophysiology
- Not reported
Neuroinflammation
- Not reported
Updated 16/05/2018