Behavioral Phenotyping in a Murine Model of -Associated Parkinson Disease.

Mutations in , the gene encoding glucocerebrosidase, are common genetic risk factors for Parkinson disease (PD). While the mechanism underlying this relationship is unclear, patients with -associated PD often have an earlier onset and faster progression than idiopathic PD. Previously, we modeled -associated PD by crossing haploinsufficient mice with mice overexpressing a human mutant α-synuclein transgene (), observing an earlier demise, shorter life span and faster symptom progression, although behavioral testing was not performed. To assess whether // mice exhibit a prodromal behavioral phenotype, we studied three cardinal PD features: olfactory discrimination, memory dysfunction, and motor function. The longitudinal performance of // ( = 8), ( = 9), ( = 10) and wildtype ( = 6) mice was evaluated between ages 8 and 23 months using the buried pellet test, novel object recognition test and the beam walk. Fifteen-month-old // mice showed more olfactory and motor deficits than wildtype mice. However, differences between // and mice generally did not reach statistical significance, possibly due to small sample sizes. Furthermore, while haploinsufficiency leads to a more rapid demise, this might not result in an earlier prodromal stage, and other factors, including aging, oxidative stress and epigenetics, may contribute to the more fulminant disease course.