Characterization of a novel mouse model of Parkinson’s disease
Objectives
The objective of this project is to characterize a new mouse model of Parkinson’s disease at the behavioral, cellular and molecular level. The pathology will be examined in the central nervous system, retina, heart and gut.
Abstract
To date, modelling Parkinson’s disease (PD)-like phenotype in rodents requires the use of toxic substances or excellent skills in stereotaxic surgery. These methods go along with variabilities in the results which limit the attractiveness of these models. In parallel, transgenic mouse models of PD only mimic pre-symptomatic forms of the disease. Hence, it is crucial to develop novel models of PD that are relevant, reproducible, and that elicit behavioral and cellular phenotypes reminiscent to the human pathology. We will take advantage of a novel viral vector allowing, via a simple systemic injection, to express a transgene throughout the central nervous system. We will combine this new tool with a genetic construct expressing human alpha-synuclein under the control of a dopamine neuron-specific promoter to induce a Parkinson-like phenotype. Behavioral tests will be used to assess locomotor and non-motor symptoms and the neuronal pathology will be studied with a broad range of histological, biochemical and molecular techniques.
Methods
The student will learn: plasmids and AAV vectors production, intravenous vector injection in mice, behavioral test (motor and cognitive tests), post-mortem analysis including histology, immunohistochemistry, confocal microscopy, western blotting, tissue clearing, light-sheet microscopy.
References
Reynaud-Dulaurier et al., (2020) Brain ; PMID : 32413099
Tamburrino et al., (2015) Acta Neuropathologica Communcations ; PMID: 26666562
Decressac et al., (2012) Science Translational Medicine ; PMID: 23220632
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