PAC-hsynA53T – Mouse

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.
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