General Information

Mouse: FVB/N x 129S6/SvEvTac

Expression of the mutant (A30P) human 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 including one in the X chromosome.

References: Kuo 2010

Transgene expression

  • 6 weeks-6 months: high but stable expression of the transgene is observed in the whole brain and distal colon.

Neurodegeneration

  • 11 and 18 months: no apparent loss of TH-positive neurons is observed in the SN.

Dopamine Homeostasis

  • 6 and 12 months: No deficits are observed.

Inclusions

  • 6-18 months: no alpha-synuclein abnormalities are observed in the brain. Inclusions are detected in the enteric nervous system.

Motor Behaviours

  • No gross motor symptoms (ataxia, tremor, paralysis) are observed at any time
  • 6-18 months: no impairments are detected in the rotarod and open field tests.

Response to L-DOPA treatment

  • Not reported

Non motor Behaviours

  • Colonic deficits: A reduction in expulsion time is observed at 6-12 months (detected only in male and not in female mice). A reduction of the amount of stool that increases with age is observed  (greater at 12 months compared to 6 months).
  • Whole-gut transit time: increase of transit time (3-12 months).
  • Olfaction: no deficits are observed.
  • Autonomic dysfunctions: no deficits are observed.

Electrophysiology

  • Not reported

Neuroinflammation

  • Not reported.

 

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