General Information
Mice: FvB
The sequence coding for the human parkin Q311X truncated protein (155aa shorter) is expressed under the control of the dopamine transporter gene promoter and using the bacterial artificial chromosome (BAC).
Endogenous Parkin: Yes
Corresponding human genotype: The G311X loss-of-function truncation in the Parkin gene is associated with a common form of autosomal recessive juvenile parkinsonism.
Targeted gene: Parkin
References: Lu 2009, Siddiqui 2015
Transgene expression
3 months: The transgene is expressed in the SN and ventral tegmental are (VTA) (up to 42% higher than the endogenous protein)
Neurodegeneration
3 months: No visible degeneration is observed.
12 months: A significant loss of TH-positive terminals is detected in the striatum
16 months: A significant loss of dopaminergic neurons is observed in the SN of transgenic mice compared to the wild type or GFP-BAC animals.
The mouse line harbouring a single copy of the G311X-BAC displays a lesser level of nigral neurodegeneration than the animals expressing two copies of the mutated gene.
Dopamine Homeostasis
19-21 months: The levels of DA and its metabolites (DOPAC) are reduced in the striatum of the transgenic animals compared to wild type littermates.
Inclusions
3 months: No inclusions are detected.
16 months: Cytoplasmic accumulation of alpha-synuclein resistant to proteinase K treatment is observed in the SN of the transgenic animals but not in the control animals.
Motor Behaviours
3-4, 12, 16-19 and 21 months: No significant alterations can be observed up to 12 months old animals. At later time points however, transgenic mice exhibit diminished performances in the cylinder, open-field, challenging transversal beam and adhesive removal tests.
Response to dopaminergic treatment
Not reported
Non-motor Behaviours
Not reported
Electrophysiology
12-14 months: No differences can be observed using cyclic voltammetry between the transgenic and control mice (Single pulse-evoked release or paired-pulse ratio).
Neuroinflammation
Not reported