BAC-hsynE46K – Rat

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.

Neurodegeneration

• 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.

Inclusions

• 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

Electrophysiology

• Not reported

Neuroinflammation

• Not reported