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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,9,24]]},"abstract":"<jats:p>\n                    Parkinson\u2019s 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\n                    <jats:italic>SNCA<\/jats:italic>\n                    , which encodes alpha-Synuclein (\u03b1-Syn), have been made, but these lines do not express\n                    <jats:italic>SNCA<\/jats:italic>\n                    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\n                    <jats:italic>SNCA<\/jats:italic>\n                    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 \u03b1-Syn in different tissues and detected phospho-\u03b1-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\n                    <jats:italic>\n                      Snca\n                      <jats:sup>G51D<\/jats:sup>\n                    <\/jats:italic>\n                    mice thus parallel the progression of human PD and will enable us to study PD pathogenesis and test future therapies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2406479121","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T15:34:47Z","timestamp":1726500887000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":15,"title":["Olfactory deficit and gastrointestinal dysfunction precede motor abnormalities in alpha-Synuclein G51D knock-in mice"],"prefix":"10.1073","volume":"121","author":[{"given":"YoungDoo","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas 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Neurological Research Institute at Texas Children\u2019s Hospital, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surabi","family":"Veeraragavan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra Rae","family":"Garza","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-5763","authenticated-orcid":false,"given":"Benjamin David Webst","family":"Belfort","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Arenkiel","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, TX 77030"},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5636-5314","authenticated-orcid":false,"given":"Rodney","family":"Samaco","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of 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