| First Author | Do J | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 13 | PubMed ID | 34202076 |
| Mgi Jnum | J:313737 | Mgi Id | MGI:6751129 |
| Doi | 10.3390/ijms22136826 | Citation | Do J, et al. (2021) Behavioral Phenotyping in a Murine Model of GBA1-Associated Parkinson Disease. Int J Mol Sci 22(13) |
| abstractText | Mutations in GBA1, the gene encoding glucocerebrosidase, are common genetic risk factors for Parkinson disease (PD). While the mechanism underlying this relationship is unclear, patients with GBA1-associated PD often have an earlier onset and faster progression than idiopathic PD. Previously, we modeled GBA1-associated PD by crossing gba haploinsufficient mice with mice overexpressing a human mutant alpha-synuclein transgene (SNCA(A53T)), observing an earlier demise, shorter life span and faster symptom progression, although behavioral testing was not performed. To assess whether gba(+)(/-)//SNCA(A53T) mice exhibit a prodromal behavioral phenotype, we studied three cardinal PD features: olfactory discrimination, memory dysfunction, and motor function. The longitudinal performance of gba(+)(/-)//SNCA(A53T) (n = 8), SNCA(A53T) (n = 9), gba(+)(/-) (n = 10) and wildtype (n = 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 gba(+)(/-)//SNCA(A53T) mice showed more olfactory and motor deficits than wildtype mice. However, differences between gba(+)(/-)//SNCA(A53T) and SNCA(A53T) mice generally did not reach statistical significance, possibly due to small sample sizes. Furthermore, while gba 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. |
