Thy1-hsynA30P – Mouse

General Information

Mouse: CB57BL/CH3

Expression of the mutant (A30P) human alpha-synuclein protein under the control of the Thy1 promoter

Endogenous mouse alpha synuclein: Yes

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

Transgene insertion:  not specified

References: Kahle 2001; Frasier 2005

Transgene expression

• 1 months: Strong expression of the transgene is observed in whole brain with a 2-4 x increase compared to endogenous alpha-synuclein. Stable high expression levels of the transgene are maintained into old age.
• 6 months: High expression of the transgene is detected in the olfactory bulb.

Neurodegeneration

• No loss of TH-positive neurons is observed

Dopamine Homeostasis

• Not reported

Inclusions

• 12 months: accumulation of abnormal alpha-synuclein protein is observed in several brain regions (superior colliculus, cerebellum, ….) but not in the striatum and SN.
• Whole brain analysis at end stage shows the presence of insoluble protein aggregates in the reticular formation and in the olfactory bulb.

Motor Behaviours

• 6-14 months: progressive motor behaviours are observed that begin with tremor and progress to muscular rigidity, postural instability, leading to paralysis that requires sacrifice of the animal at end stage.

Response to L-DOPA treatment

• Not reported

Non motor Behaviours

6 months: Hyposnia. Impairment in fine but not in pure and general odour discrimination is observed. The olfactory memory is not affected.

Electrophysiology

• Not reported

Neuroinflammation

• Not reported