{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:02:26Z","timestamp":1788238946860,"version":"build-2803163510"},"reference-count":61,"publisher":"National Academy of Sciences","issue":"6","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"HHS | NIH | National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01 ES024812"],"award-info":[{"award-number":["R01 ES024812"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"HHS | NIH | National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01 ES031574"],"award-info":[{"award-number":["R01 ES031574"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"HHS | NIH | National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["F31-ES036908"],"award-info":[{"award-number":["F31-ES036908"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,2,10]]},"abstract":"<jats:p>\n                    Essential metals accumulate in the basal ganglia at elevated levels and induce incurable motor disease. But, unlike other motor diseases, the neuronal targets of essential metals are unknown, and this fundamental knowledge gap has limited therapeutic progress. Because metal efflux transporters have high specificity, we hypothesized that neuron-specific knockout or knockin (i.e., overexpression) of efflux transporters may alter metal levels in targeted neurons and define the neuronal targets of metal-induced disease. To test this, we focused on manganese (Mn)-induced motor disease, which is a public health problem. We generated six neuron-specific\n                    <jats:italic toggle=\"yes\">Slc30a10<\/jats:italic>\n                    mouse strains with knockout or knockin of the Mn efflux transporter\n                    <jats:italic toggle=\"yes\">Slc30a10<\/jats:italic>\n                    in dopaminergic, GABAergic, or glutamatergic neurons. In the knockout strains, SLC30A10 was depleted and Mn levels were elevated in targeted brain regions. However, only dopaminergic- or glutamatergic-, but not GABAergic-, specific knockouts developed motor deficits without Mn exposure. Conversely, in the knockins, SLC30A10 was elevated and the increase in Mn levels after Mn exposure was attenuated in targeted regions. However, only dopaminergic- or glutamatergic-, but not GABAergic-, specific knockins were protected against Mn-induced motor deficits. Dopaminergic-specific\n                    <jats:italic toggle=\"yes\">Slc30a10<\/jats:italic>\n                    knockouts also exhibited deficits in dopaminergic neurotransmission that were consistent with their motor phenotype. Overall, 1) elevated Mn targets dopaminergic and glutamatergic neurons to induce motor disease, and 2) neuron-specific knockout\/knockin of efflux transporters is an effective strategy to isolate the neuronal targets and underlying mechanisms of metal-induced neurological disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2515785123","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T20:07:36Z","timestamp":1770062856000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Neuron-specific modulation of SLC30A10 identifies dopaminergic and glutamatergic neurons as targets of manganese-induced motor disease"],"prefix":"10.1073","volume":"123","author":[{"given":"Stephanie M.","family":"Grant","sequence":"first","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin","place":["Austin"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8728-8813","authenticated-orcid":false,"given":"Ashvini","family":"Melkote","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin","place":["Austin"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2327-5771","authenticated-orcid":false,"given":"Mollie X.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Washington","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7264-904X","authenticated-orcid":false,"given":"Thomas","family":"Jursa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Environmental Toxicology, University of California at Santa Cruz","place":["Santa Cruz"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherish A.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin","place":["Austin"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Hutchens","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin","place":["Austin"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3539-7366","authenticated-orcid":false,"given":"William","family":"Shawlot","sequence":"additional","affiliation":[{"name":"Mouse Genetic Engineering Facility, Center for Biomedical Research Support, University of Texas at Austin","place":["Austin"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3465-5331","authenticated-orcid":false,"given":"Larry S.","family":"Zweifel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Washington","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rueben A.","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin","place":["Austin"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald R.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Environmental Toxicology, University of California at Santa Cruz","place":["Santa Cruz"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3420-7830","authenticated-orcid":false,"given":"Somshuvra","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin","place":["Austin"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70190-5"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.2030"},{"key":"e_1_3_4_3_2","unstructured":"A. Gregory M. A. Kurian J. Wilson S. Hayflick \u201cNeurodegeneration with Brain Iron Accumulation Disorders Overview\u201d in GeneReviews M. P. Adam Eds. (University of Washington Seattle WA 1993)."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxaa066"},{"key":"e_1_3_4_5_2","unstructured":"J. Immergluck L. M. Grant A. C. Anilkumar Wilson Disease. StatPearls Treasure Island (FL)(2025)."},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-061010-113641"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22062"},{"key":"e_1_3_4_8_2","first-page":"51","article-title":"The basal ganglia and disorders of movement: Pathophysiological mechanisms","volume":"17","author":"Obeso J. A.","year":"2002","unstructured":"J. A. Obeso, M. C. Rodriguez-Oroz, M. Rodriguez, J. Arbizu, J. M. Gimenez-Amaya, The basal ganglia and disorders of movement: Pathophysiological mechanisms. News Physiol. 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A. G. S. Taylor Activity of the manganese efflux transporter SLC30A10 in dopaminergic but not GABAergic neurons protects against neurotoxicity. bioRxiv [Preprint] (2022) https:\/\/doi.org\/10.1101\/2022.02.21.481385. 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