General Information

Mouse: CB57BL/J6

Expression of the double mutant A53T+A30P human alpha-synuclein under the control of the rat tyrosine hydroxylase (TH) promoter.

Endogenous mouse alpha synuclein: Yes

Corresponding human genotype: not present

Transgene insertion: not specified

References: Richfield 2002; Thiruchelvam 2004; Su 2009

Transgene expression

  • 2-3 months: high transgene expression is observed in the SN (cell bodies), striatum (terminals), eye, locus ceruleus. Expression of human alpha-synuclein is about 25% of that of endogenous mouse alpha synuclein.


  • No loss of TH-positive neurons is detected but abnormal axons appearance of the medial forebrain bundle is observed. Increased in DAT density and increased vulnerability to MPTP treatment is observed.

Dopamine Homeostasis

  • Up to 23 months: No changes in dopamine and dopamine metabolites are detected


  • No inclusions are observed

Motor Behaviours

  • 2-3 months: Some signs of spontaneous motor hyperactivity are observed. A reduced motor response (horizontal activity) to repeated amphetamine injection is detected. A greater decrease in motor activity following MPTP treatment is observed in the mutant mice compared to non transgenic littermates.
  • From 7 to 23 months: No significant differences are observed in spontaneous locomotor activities at any age

Response to L-DOPA treatment

  • Not reported

Non motor Behaviours

  • Not reported


  • Not reported


  • 1 months: Increased levels of activated microglia are observed in the SN and striatum. A 2-4x increase in the levels of several soluble factors is observed. This increase resolves with aging (PMID 19526281)
  • 6 months: Complete resolution of microglia activation is observed
  • 12 months: no microglia activation is detected. Interestingly, non-transgenic littermate display increased microglial activation at this age.

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