General Information
Mouse: CB57BL/6
Expression of the human wild type alpha-synuclein protein under the control of the Thy1 promoter
Endogenous mouse alpha synuclein: Yes
Corresponding human genotype: Autosomal dominant mutation in PD patients (PARK1)
Transgene insertion: not reported
References: Chesselet 2012 ; Martin 2014
Transgene expression
- 6-12 months : strong expression of the mutated hasynA53T throughout the brain (cortex, olfactory bulb, striatum, cerebellum, diencephalon as well as a strong expression) as well as in spinal cord and motor neuron.
Neurodegeneration
- Age-related loss of TH-positive neurons in the SN and the striatum reaching 60% at endstage (12 months)
- Age-related degeneration of striatal and cerebellum interneurons
- 8-12 months: age-related degeneration of cerebral cortex (strong), hippocampus (moderate), striatal and cerebellum interneurons, and motor thalamus.
Dopamine Homeostasis
- Not reported
Inclusions
- 6 months: aggregates observed mainly in the spinal cord brainstem, hippocampus and cerebellum.
- 8-12 months: inclusions detected in all brain regions
Motor Behaviours
- 2-4 months: normal spontaneous motor activity compared to control littermates (PMID 24325796)
- 6 months : motor deficits (spasticity, tremors)
- 8 months: rigidity, bradykinesia and gait abnormalities
- 12 months : complete immobility and death (usually between 10-12 months).
Response to L-DOPA treatment
- Not reported
Non motor Behaviours
- Not reported
Electrophysiology
- Not reported
Neuroinflammation
- Not reported