General Information

Mouse: C57BL/6 x 129/SvEv^Brd

Mice in which exons 4-5 of the PINK1 gene have been deleted by insertion of a neo probe (PGK-neo-pA) using homologous recombination. This insertion removes the N-terminal portion of the PINK1 protein that contains the kinase activity causing loss of function.

Corresponding human genotype: Autosomal recessive mutation in the PINK1 gene causing a loss-of-function of the protein and leading to early-onset Parkinson’s disease (PARK6).

Mutated gene: PINK1

References: Akundi 2011

Loss of dopaminergic neurons

• 12 months: apparent reduction in the number of TH-positive neurons in the SN. This decrease is accompanied by an increase of phosphorylated c-Jun protein in dopaminergic neurons.

Dopamine Homeostasis

• 2 months: no changes in dopamine levels and dopamine turnover are detected in the striatum
• 6–12 months: reduction of dopamine levels in the striatum (levels are about 75% those measured in wild type mice). An increase in dopamine turnover is detected in the striatum.

Inclusions

• Not reported

Motor Behaviours

• Not reported

Response to dopaminergic treatment

• Not reported

Non motor Behaviours

• Not reported

Electrophysiology

• Not reported

Neuroinflammation

6 months: increased levels of cytokine (IL-1beta, IL-10 and IL-12) in the striatum in response to a peripheral inflammatory stimuli (LPS) suggesting an enhanced susceptibility to inflammation.