General Information

Mouse: CB57BL/6J

Expression of the human C-terminal-truncated (1-130) mutant A53T alpha-synuclein under the control of the rat tyrosine hydroxylase (TH) promoter.

Endogenous mouse alpha synuclein: Yes

Corresponding human genotype: The A53T mutation causes an autonomous dominant form of the disease. Truncated alpha-synuclein is enriched in human Lewy body extracts

Transgene insertion:  not specified

References: Wakamatsu 2008a; Wakamatsu 2008b

Transgene expression

  • 6 weeks – 52 weeks: transgene expression is observed in the midbrain at reduced levels (30-60%) compared to those of endogenous alpha-synuclein. Alpha-synuclein protein is observed in the soma and nuclei of neurons.

Neurodegeneration

  • 8, 26 and 52 weeks: significant loss (20-45%) of TH-positive neurons is observed in the SN. This loss is observed at 8 weeks and remains stable for up to 52 weeks. A 50% reduction of TH is observed in the striatum at 8 and 52 weeks of age.

Dopamine Homeostasis

  • 8 and 52 weeks: Both dopamine and homovanillic acid levels are significantly reduced in the striatum

Inclusions

  • Not reported

Motor Behaviours

  • 8 and 52 weeks: reduction in spontaneous locomotor activity.
  • 8 and 52 weeks: no deficits are observed in the rotarod, pole, traction or catalepsy tests.

Response to L-DOPA treatment

  • 8 and 52 weeks: Treatment with L-DOPA or dopamine receptor agonists (quinpirole, talipexole, pergolide) induce recovery of spontaneous locomotor activity

Non motor Behaviours

  • Not reported

Electrophysiology

  • Not reported

Neuroinflammation

  • Not reported

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