General Information

Rat: Sprague-Dawley

Expression of the mutant (E46K) human alpha-synuclein protein using the bacterial artificial chromosome (BAC) in rat.

Endogenous rat alpha synuclein: Yes

Corresponding human genotype: Autosomal dominant mutation in PD patients

Transgene insertion:  chromosome 11

Reference: Cannon 2013

Transgene expression

  • 12 months: diffuse expression of the transgene is observed throughout the brain, in particular in the olfactory bulb, frontal cortex, striatum, ventral midbrain and cerebral cortex. A low expression is also detected in the spinal cord.


  • 6 months: Increased sensitivity of dopaminergic terminals (but not of neurons) to low-dose rotenone treatment is detected.
  • 12 months: No changes in DAT density is observed suggesting that there is no nigral neurodegeneration.

Dopamine Homeostasis

  • 12 months: no depletion of dopamine is observed; a reduction in the levels of dopamine metabolites indicates a decrease in dopamine turnover. Reduced serotoninergic turnover is also detected.


  • 12 months: accumulation of abnormal alpha-synuclein is detected in TH-positive neurons in the SN and VTA, striatum (in processes), cortex (in processes). Intracellular accumulation seems limited to dopaminergic neurons.

Motor Behaviours

  • Not reported

Response to L-DOPA treatment

  • Not reported

Non motor Behaviours

  • Not reported


  • Not reported


  • Not reported



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