TH-hsynwt(1-120)- Mouse

General Information

Mouse: (CB57BL/6J X CBA/ca) X Syn^-/-CB57BL/6JOla

Expression of human C-terminal-truncated (1-120) wild type alpha-synuclein under the control of the rat tyrosine hydroxylase (TH) promoter.

Endogenous rat alpha synuclein: No (backcrossed to CB57BL/6JOla lacking alpha-synuclein)

Corresponding human genotype: Not reported but truncated alpha-synuclein is enriched in human Lewy body extracts

Transgene insertion:  not specified

References:  Tofaris 2006; Michell 2007

Transgene expression

• 6 weeks – 14 months: High transgene expression is observed in SN and olfactory bulb. Protein expression is observed in the somatodendritic compartment of TH-positive neurons (SN) and in terminals (striatum). Truncated alpha-synuclein expression is also observed in the locus ceruleus.

Neurodegeneration

• Up to 14 months: No loss of TH-positive neurons is detected.

Dopamine Homeostasis

• 1 months: No changes in striatal dopamine levels
• 2-12 months: 30% reduction of dopamine and homovanillic acid levels are observed in the striatum

Inclusions

• Up to 12 months: Inclusions positive for the truncated alpha-synuclein are observed in the olfactory bulb at all ages.
• 12-14 months: perinuclear inclusion of truncated alpha-synuclein is observed in the SN.

Motor Behaviours

• 6 months: No significant changes in total spontaneous activity are detected
• 18 months: Reduced spontaneous activity is observed.

Response to L-DOPA treatment

• Not reported

Non motor Behaviours

• Not reported

Electrophysiology

• Not reported

Neuroinflammation

• Up to 14 months: Progressive increase of inflammatory response is observed