General Information
Mice: C57BL/6
The exon 2 of the Parkin gene is replaced by the coding sequence of the GFP or neo gene.
The animals described here are homozygous knockout mice.
Endogenous Parkin: No
Corresponding human genotype: The deletion, duplication or triplication of exons 2 of the Parkin gene is associated with Parkinson’s disease.
Targeted gene: PARKIN
References: Perez 2005, Perez 2005, Sato 2006
Transgene expression
Absence of Parkin expression is confirmed by western blot.
Neurodegeneration
Up to 22 months: No visible degeneration can be observed in the SN of the PARKIN knock out mice. Interestingly, the knock out mice are more sensitive when exposed to 6-OHDA toxin.
Dopamine Homeostasis
12 and 22 months: The level of DA is elevated in the midbrain of the transgenic animals at 12 months. Levels of DA metabolites (DOPAC or HVA) are comparable to those measured in control mice (HPLC). No differences are observed in striatal levels of DA, DOPAC or HVA.
The binding index of the dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) remain unchanged in the striatum of the KO mice.
The binding level of D1 and D2 receptors is higher in the striatum of transgenic animals compared to that observed in control mice.
DA synthesis and release is reduced in the striatum of transgenic animals.
Inclusions
22 months: Striatal and cortical levels of ubiquitin and alpha-synuclein are similar between the transgenic and control animals.
Motor Behaviours
3, 6, 12 and 18-22 months: No major alterations are observed in the gait analysis or open field test. Performances of KO mice on the rotarod, inverted wire grid, pole and balance beams are comparable to the wild type mice.
Response to dopaminergic treatment
Not reported
Non-motor Behaviours
12 and 18-22 months: Somatosensory functions are comparable between transgenic and control animals (adhesive removal, tail-flick and nociception tests). KO animals do not exhibit anxiety or depression-like behaviour (like-dark exploration, evaluate plus maze, forced-swim and tail-suspension tests). Similarly, learning and memory abilities of the transgenic mice are comparable to the wild type animals (T-maze alternation task, water mazes and passive-avoidance test).
Electrophysiology
Not reported
Neuroinflammation
Not reported