1. Olfactory deficit and gastrointestinal dysfunction precede motor abnormalities in alpha-Synuclein G51D knock-in mice.
- Author
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YoungDoo Kim, McInnes, Joseph, Jiyoen Kim, Yan Hong Wei Liang, Veeraragavan, Surabi, Garza, Alexandra Rae, Belfort, Benjamin David Webst, Arenkiel, Benjamin, Samaco, Rodney, and Zoghbi, Huda Yahya
- Subjects
ENTERIC nervous system ,PARKINSON'S disease ,TRANSGENIC mice ,OLFACTORY bulb ,SMELL disorders - Abstract
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 (a-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 a-Syn in different tissues and detected phospho-a-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 SncaG51D mice thus parallel the progression of human PD and will enable us to study PD pathogenesis and test future therapies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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