BAC-hsynA30P – Mouse

General Information

Mouse: asyn^-/- CB57BL6

Expression of the mutated (A30P) human alpha-synuclein protein using the bacterial artificial chromosome (BAC).

Endogenous alpha-synuclein: No

Corresponding human genotype: Autosomal dominant mutation in PD patients (PARK1/PARK4)

Transgene insertion: chromosome 15

References:  Abellovich 2000; Taylor 2014,

Transgene expression

• 3 months: Transgene expression is observed in the cortex, as well as in TH-positive neurons in the SN and VTA.
• Expression of transgene restores sensitivity to MPTP treatment which is usually absent in mice lacking endogenous alpha-synuclein.

Neurodegeneration

• Up to 18 months: No neurodegeneration is observed in transgenic mice.

Dopamine Homeostasis

• Up to 24 months: no loss of dopamine is detected in the SN and locus coeruleus.
• 3 months: a decrease in evoked dopamine release is observed in the striatum.

Inclusions

• Up to 24 months: no pathological expression of alpha-synuclein is observed

Motor Behaviours

Test results from BAC-hsynA30P mice are compared to those of wild type animals lacking endogenous alpha-synuclein

• Up to 18 months: no novelty-induced motor deficits and no changes in forepaw stride length are observed. No deficits in rotarod test are present.

Response to L-DOPA treatment

• Not reported

Non motor Behaviours

Tests results from BAC-hsynA30P mice are compared to those of wild type animals lacking endogenous alpha-synuclein

• No anxiety-type phenotype is observed
• No differences in circadian rhythm activity are detected although a specific increase in wheel running at dark can be detected.
• Gastrointestinal disturbances are not detected.

Electrophysiology

• Not reported

Neuroinflammation

• Up to 24 months: No gliosis is observed