General Information
Mouse: CB57BL/CH3
Expression of the mutant (A30P) human 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/PARK4)
Transgene insertion: not specified
References: Kahle 2001; Frasier 2005
Transgene expression
- 1 months: Strong expression of the transgene is observed in whole brain with a 2-4 x increase compared to endogenous alpha-synuclein. Stable high expression levels of the transgene are maintained into old age.
- 6 months: High expression of the transgene is detected in the olfactory bulb.
Neurodegeneration
- No loss of TH-positive neurons is observed
Dopamine Homeostasis
- Not reported
Inclusions
- 12 months: accumulation of abnormal alpha-synuclein protein is observed in several brain regions (superior colliculus, cerebellum, ….) but not in the striatum and SN.
- Whole brain analysis at end stage shows the presence of insoluble protein aggregates in the reticular formation and in the olfactory bulb.
Motor Behaviours
- 6-14 months: progressive motor behaviours are observed that begin with tremor and progress to muscular rigidity, postural instability, leading to paralysis that requires sacrifice of the animal at end stage.
Response to L-DOPA treatment
- Not reported
Non motor Behaviours
6 months: Hyposnia. Impairment in fine but not in pure and general odour discrimination is observed. The olfactory memory is not affected.
Electrophysiology
- Not reported
Neuroinflammation
- Not reported