| First Author | Kim Y | Year | 2024 |
| Journal | Proc Natl Acad Sci U S A | Volume | 121 |
| Issue | 39 | Pages | e2406479121 |
| PubMed ID | 39284050 | Mgi Jnum | J:354987 |
| Mgi Id | MGI:7737604 | Doi | 10.1073/pnas.2406479121 |
| Citation | Kim Y, et al. (2024) Olfactory deficit and gastrointestinal dysfunction precede motor abnormalities in alpha-Synuclein G51D knock-in mice. Proc Natl Acad Sci U S A 121(39):e2406479121 |
| abstractText | Parkinson's disease (PD) is typically a sporadic late-onset disorder, which has made it difficult to model in mice. Several transgenic mouse models bearing mutations in SNCA, which encodes alpha-Synuclein (alpha-Syn), have been made, but these lines do not express SNCA in a physiologically accurate spatiotemporal pattern, which limits the ability of the mice to recapitulate the features of human PD. Here, we generated knock-in mice bearing the G51D SNCA mutation. After establishing that their motor symptoms begin at 9 mo of age, we then sought earlier pathologies. We assessed the phosphorylation at Serine 129 of alpha-Syn in different tissues and detected phospho-alpha-Syn in the olfactory bulb and enteric nervous system at 3 mo of age. Olfactory deficit and impaired gut transit followed at 6 mo, preceding motor symptoms. The Snca(G51D) mice thus parallel the progression of human PD and will enable us to study PD pathogenesis and test future therapies. |
