{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:44:49Z","timestamp":1790131489584,"version":"4.0.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"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":"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"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Elevated manganese (Mn) accumulates in the brain and induces neurotoxicity. SLC30A10 is an Mn efflux transporter that controls body Mn levels. We previously reported that full-body Slc30a10 knockout mice (1) recapitulate the body Mn retention phenotype of humans with loss-of-function SLC30A10 mutations and (2) unexpectedly develop hypothyroidism induced by Mn accumulation in the thyroid, which reduces intra-thyroid thyroxine. Subsequent analyses of National Health and Nutrition Examination Survey data identified an association between serum Mn and subclinical thyroid changes. The emergence of thyroid deficits as a feature of Mn toxicity suggests that changes in thyroid function may be an underappreciated, but critical, modulator of Mn-induced disease. To better understand the relationship between thyroid function and Mn toxicity, here we further defined the mechanism of Mn-induced hypothyroidism using mouse and rat models. Slc30a10 knockout mice exhibited a profound deficit in thyroid iodine levels that occurred contemporaneously with increases in thyroid Mn levels and preceded the onset of overt hypothyroidism. Wild-type Mn-exposed mice also exhibited increased thyroid Mn levels, an inverse correlation between thyroid Mn and iodine levels, and subclinical hypothyroidism. In contrast, thyroid iodine levels were unaltered in newly generated Slc30a10 knockout rats despite an increase in thyroid Mn levels, and the knockout rats were euthyroid. Thus, Mn-induced thyroid dysfunction in genetic or Mn exposure-induced mouse models occurs due to a reduction in thyroid iodine subsequent to an increase in thyroid Mn levels. Moreover, rat and mouse thyroids have differential sensitivities to Mn, which may impact the manifestations of Mn-induced disease in these routinely used animal models.<\/jats:p>","DOI":"10.1093\/mtomcs\/mfae029","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T02:40:28Z","timestamp":1718246428000},"source":"Crossref","is-referenced-by-count":8,"title":["Elevated thyroid manganese reduces thyroid iodine to induce hypothyroidism in mice, but not rats, lacking SLC30A10 transporter"],"prefix":"10.1093","volume":"16","author":[{"given":"Steven","family":"Hutchens","sequence":"first","affiliation":[{"name":"Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin , Austin, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashvini","family":"Melkote","sequence":"additional","affiliation":[{"name":"Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin , Austin, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Jursa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Environmental Toxicology, University of California at Santa Cruz , Santa Cruz, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Shawlot","sequence":"additional","affiliation":[{"name":"Mouse Genetic Engineering Facility, The University of Texas at Austin , Austin, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-597X","authenticated-orcid":false,"given":"Leonardo","family":"Trasande","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Environmental Pediatrics and Departments of Population Health and Environmental Medicine, New York University Grossman School of Medicine , New York, NY, \u00a0 USA"},{"name":"New York University Wagner School of Public Service , New York, NY, \u00a0 USA"},{"name":"New York University College of Global Public Health , New York, NY, \u00a0 USA"}],"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 , Santa Cruz, CA , USA"}],"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 & Toxicology, College of Pharmacy, The University of Texas at Austin , Austin, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"issue":"6","key":"2024070115191294600_bib1","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1093\/jn\/nxaa066","article-title":"Maintaining translational relevance in animal models of manganese neurotoxicity","volume":"150","author":"Taylor","year":"2020","journal-title":"J. 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