{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T11:05:38Z","timestamp":1770548738586,"version":"3.49.0"},"reference-count":36,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK123113"],"award-info":[{"award-number":["R01DK123113"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As a newly identified manganese transport protein, ZIP14 is highly expressed in the small intestine and liver, which are the two principal organs involved in regulating systemic manganese homeostasis. Loss of ZIP14 function leads to manganese overload in both humans and mice. Excess manganese in the body primarily affects the central nervous system, resulting in irreversible neurological disorders. Therefore, to prevent the onset of brain manganese accumulation becomes critical. In this study, we used Zip14\u2212\/\u2212 mice as a model for ZIP14 deficiency and discovered that these mice were born without manganese loading in the brain, but started to hyper-accumulate manganese within 3 weeks after birth. We demonstrated that decreasing manganese intake in Zip14\u2212\/\u2212 mice was effective in preventing manganese overload that typically occurs in these animals. Our results provide important insight into future studies that are targeted to reduce the onset of manganese accumulation associated with ZIP14 dysfunction in humans.<\/jats:p>","DOI":"10.3390\/ijms22136773","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T04:24:36Z","timestamp":1624508676000},"page":"6773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Restriction of Manganese Intake Prevents the Onset of Brain Manganese Overload in Zip14\u2212\/\u2212 Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Yuze","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences, The University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guojun","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, The University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningning","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, The University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"C862","DOI":"10.1152\/ajpcell.00479.2010","article-title":"Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron","volume":"301","author":"Sparkman","year":"2011","journal-title":"Am. 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