General Information

Mice:  C57BL/6

Conditional expression of the full-length human wild type LRRK2 protein was achieved through crossing of heterozygous knockin mice, expressing the tetracycline transactivatior (tTA) under the control of a Pitx3-IRES2 sequence (Pitx3), with mice expressing the 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: LRRK2 is the greatest known genetic contributor to Parkinson’s disease.

 Targeted gene: LRRK2

References: Liu 2015

Transgene expression

• Postnatal day 1: No expression of the transgene is detected.
• 1 month: Expression of the human wild type LRRK2 protein seems restricted to SN dopaminergic neurons (4 fold increase compared to control mice). Administration of doxycycline supresses expression of the transgene.

Neurodegeneration

• Up to 20 months: No obvious neurodegeneration is observed in the SN or ventral tegmental area of the transgenic animals. Similarly, no changes are detected in the density of TH-positive axons present in the striatum.

Dopamine Homeostasis

• 1 and 12 months: Elevated level of DA is measured in the striatum of the transgenic animals.

Inclusions

• Not reported

Motor Behaviours

• 2, 6, 12 and 18 months: Except a slight increase in vertical and horizontal activity in the open field, no differences can be observed in these transgenic animals compared to control littermates (rotator and gait analysis).

Response to dopaminergic treatment

• Not reported

Non-motor Behaviours

• Not reported

Electrophysiology

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

Neuroinflammation

• Not reported

Updated 16/05/2018