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.
Neurodegeneration
- 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
Inclusions
- 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
Electrophysiology
- Not reported
Neuroinflammation
- 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.