General Information
Mouse: FVB/N x 129S6/SvEvTac
Expression of the human mutant (A53T) alpha-synuclein protein using the P1 artificial chromosome (PAC).
Endogenous alpha-synuclein: No
Corresponding human genotype: Autosomal dominant mutation in PD patients (PARK1/PARK4)
Transgene insertion: 4 chromosomal insertions
Reference: Kuo 2010
Transgene expression
- 6 weeks-6 months: high (2-8 x) but stable transgene expression is observed in the whole brain and distal colon.
Neurodegeneration
- 11 and 18 months: no evident loss of TH-positive neurons is observed in the SN
Dopamine Homeostasis
- 11 and 18 months: No deficits are observed
Inclusions
- 6-18 months: no alpha-synuclein abnormalities are detected in the brain. Inclusions are observed in the enteric nervous system
Motor Behaviours
- No gross motor symptoms (ataxia, tremor, paralysis) can be observed at any time
- 6-12 months: a reduced latency in the rotarod test indicative of motor impairment is present . Reduced distance travelled is detected in the open field test
- 18 months: increased impairment in rotarod test and reduced distance in the open field test are observed. This later impairment is not due to a reduced exploratory behaviour (increased anxiety is not observed in this model)
Response to L-DOPA treatment
- Not reported
Non motor Behaviours
- Colonic deficits: Reduction in expulsion time is observed at 3-18 months. This reduction is higher in male when compared to female. Reduction of the amount of stool that increases with age is observed (greater at 12 months compared to 6 months).
- Whole-gut transit time: time-dependent increase (3-18 months) of transit time
- Olfaction: no deficits are observed.
- Autonomic dysfunctions: no deficits are observed
Electrophysiology
- Not reported.
Neuroinflammation
- Not reported.