Investigating the Multiple Hit hypothesis of Parkinson disease using transgenic LRRK2-R1441G rats
Master of Science
Dr. Susanne Schmid
The ‘multiple hit’ hypothesis of Parkinson disease (PD) suggests that the combination of several risk factors leads to the development of PD. Here, we explore the interaction between two potential causes of PD; a genetic mutation in the leucine-rich repeat kinase 2 (LRRK2) gene and exposure to the neurotoxin, Paraquat. This project characterizes transgenic BAC rats expressing human LRRK2 bearing the familial PD mutation, R1441G. These rats were tested for PD-related deficits at 3, 6, 9 & 12 months. These rats were then exposed to intraperitoneal injections of Paraquat. We hypothesized that LRRK2R1441G rats will show increased vulnerability to Paraquat compared to wildtype controls. Our results showed that LRRK2R1441G rats are not significantly different from wildtype rats by the 12 month stage, suggesting that this mutation alone is insufficient to manifest PD-like features in rats. In addition LRRK2R1441G rats failed to show increased vulnerability to Paraquat administration.
Shaikh, Komal T., "Investigating the Multiple Hit hypothesis of Parkinson disease using transgenic LRRK2-R1441G rats" (2014). Electronic Thesis and Dissertation Repository. 2333.