General Information

Mice:  C57BL/6

Conditional expression of the full-length human wild type LRRK2 protein was achieved using a Ca2+/calmodulin-dependent protein kinase II alpha (CaM) promoter to control the expression of the tetracycline-transactivator (tTA).

Note: In this tet-off system, the animals express the transgene in absence of tetracycline or doxycycline treatment. Keeping the animals under treatment during development prevents transgene expression and prevents possible compensation mechanisms to take place.

Endogenous LRRK2: yes

Corresponding human genotype: LRRK2 is the greatest known genetic contributor to Parkinson’s disease.

Targeted gene: LRRK2

References: Lin 2009

Transgene expression

Note: Animals are kept under doxycycline treatment until the pups are weaned (at about 2months of age)

  • 1 months: The expression of the human LRRK2 transgene is 8-16 fold higher than the endogenous mouse protein. Expression is observed mainly in the cortex and striatum. Only about 5% of midbrain neurons express the transgene.

Neurodegeneration

  • Up to 20 months: No obvious neurodegeneration is observed in the SN

Dopamine Homeostasis

  • Not reported

Inclusions

  • Not reported

Motor Behaviours

  • 2 and 6 months: No differences can be observed in transgenic animals compared to control littermates (open field and rotarod tests).

Response to dopaminergic treatment

  • Not reported

Non-motor Behaviours

  • Not reported

Electrophysiology

  • Not reported

Neuroinflammation

  • Not reported

Updated 16/05/2018