| First Author | Hansen C | Year | 2013 |
| Journal | Neurobiol Dis | Volume | 56 |
| Pages | 145-55 | PubMed ID | 23643841 |
| Mgi Jnum | J:197984 | Mgi Id | MGI:5495060 |
| Doi | 10.1016/j.nbd.2013.04.017 | Citation | Hansen C, et al. (2013) A novel alpha-synuclein-GFP mouse model displays progressive motor impairment, olfactory dysfunction and accumulation of alpha-synuclein-GFP. Neurobiol Dis 56:145-55 |
| abstractText | Compelling evidence suggests that accumulation and aggregation of alpha-synuclein (alpha-syn) contribute to the pathogenesis of Parkinson's disease (PD). Here, we describe a novel Bacterial Artificial Chromosome (BAC) transgenic model, in which we have expressed wild-type human alpha-syn fused to green fluorescent protein (GFP), under control of the mouse alpha-syn promoter. We observed a widespread and high expression of alpha-syn-GFP in multiple brain regions, including the dopaminergic neurons of the substantia nigra pars compacta (SNpc) and the ventral tegmental area, the olfactory bulb as well as in neocortical neurons. With increasing age, transgenic mice exhibited reductions in amphetamine-induced locomotor activity in the open field, impaired rotarod performance and a reduced striatal dopamine release, as measured by amperometry. In addition, they progressively developed deficits in an odor discrimination test. Western blot analysis revealed that alpha-syn-GFP and phospho-alpha-syn levels increased in multiple brain regions, as the mice grew older. Further, we observed, by immunohistochemical staining for phospho-alpha-syn and in vivo by two-photon microscopy, the formation of alpha-syn aggregates as the mice aged. The latter illustrates that the model can be used to track alpha-syn aggregation in vivo. In summary, this novel BAC alpha-syn-GFP model mimics a unique set of aspects of PD progression combined with the possibility of tracking alpha-syn aggregation in neocortex of living mice. Therefore, this alpha-syn-GFP-mouse model can provide a powerful tool that will facilitate the study of alpha-syn biology and its involvement in PD pathogenesis. |
