Parkinson’s disease is a movement disorder characterized by nigrostriatal dopamine pathway degeneration and neuronal α-synuclein accumulation. Pathogenesis is associated with mutations in α-synuclein and Gba1 encoding alleles. Animal models created to date do not recapitulate the spectrum of clinical disease features. This thesis characterizes the bi-genic Synergy mouse, hypothesized to demonstrate motor behavioural and histological abnormalities downstream of α-synuclein overexpression and mutated Gba1. Synergy and SNCA mice (overexpressed α-synuclein with wild-type Gba1) have early onset deficits in motor coordination, muscle strength and nest building. Both exhibit increased α-synuclein concentration in the brain and cerebellar inclusions positive for two markers of pathological α-synuclein processing. Overall mutant Gba1 expression within Synergy mice does not worsen the behaviour or the histopathological findings associated with overexpression of human α-synuclein in SNCA mice. Future studies will determine whether mutant Gba1 expression alters cognitive behaviour and/or lipid homeostasis in this new bi-genic model of Parkinson’s disease.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/35689 |
| Date | January 2017 |
| Creators | Fitzpatrick, Megan E. |
| Contributors | Schlossmacher, Michael, Lagace, Diane |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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