AAV A53T α-Synuclein Mouse Model of Parkinson's Disease
Injection of A53T SNCA AAV vectors to generate synuclein aggregates, neuroinflammation, neurodegeneration & dopaminergic denervation with motor deficits.
AAV Synuclein (AAV-Syn) Model Overview
For this Parkinson's disease model, we perform unilateral stereotaxic inoculation of AAVs overexpressing A53T mutant human alpha-synuclein into the substantia nigra of C57BL/6 mice at ~3 months-of-age. This mouse model reproduces several key features of human Parkinson's disease, including:
- A high degree of loss of dopaminergic neurons in the substantia nigra pars compacta
- Dopaminergic denervation of the ipsilateral striatum
- Aggregates of phosphorylated alpha-synuclein in cell bodies and neurites
- Activated microglia (Read More in our Presentation - Microglial Activation in an α-Synuclein Mouse Model of Parkinson's Disease)
- Reactive astrocytes
- Motor dysfunction
AAV-Syn Model Generation
A general schema for the model generation is:
For this specific model, we use C57BL/6 mice at ~12 weeks-of-age. We then perform stereotaxic injection of AAV vectors into the vicinity of the substantia nigra. We use digital stereotaxic devices with automated microinjectors for high accuracy & precision.
Studies using this model can be rapidly initiated. The in vivo phase of the study typically lasts ~10-12 weeks. As such, generation of readouts can be provided in a relatively short time frame, especially compared to conventional alpha-synuclein transgenic models of Parkinson's disease.
Our Validated Measures
- Rotarod test
- Cylinder test
- Tail suspension swing test
- Hindlimb clasping test
- IHC & multiplex immunofluorescence
Microscopy Images
The Interactive Image Viewer below allows you to explore an entire Multiplex Immunofluorescence tissue section from our AAV-Syn mouse model.
You can pan around the image using the left mouse button. You can zoom in and out using the mouse/trackpad (up/down) or the + and - buttons in the upper left corner. You can toggle (on/off), change color, and adjust image settings for the channels and segmentations in the Control Panel in the upper right corner. You can change tissue sections using the Section Slider in the Control Panel.
Multiplex immunofluorescence tissue section that demonstrates phosphorylated α-synuclein aggregates, activated microglia, and dopaminergic neuron loss ipsilateral to AAV-Syn injection into the substantia nigra (left hemisphere) in a C57BL/6 mouse.
Learn more about our characterization of this model and our validated measures.
Discover more of our Parkinson's Disease Models
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