{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:47:53Z","timestamp":1791978473003,"version":"4.4.0"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","award":["R01DK123113"],"award-info":[{"award-number":["R01DK123113"]}]},{"DOI":"10.13039\/100000062","name":"Office of Dietary Supplements (ODS) of the National Institutes of Health (NIH)","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>ZIP14 is a newly identified manganese transporter with high levels of expression in the small intestine and the liver. Loss-of-function mutations in ZIP14 can lead to systemic manganese overload, which primarily affects the central nervous system, causing neurological disorders. To elucidate the roles of intestinal ZIP14 and hepatic ZIP14 in maintaining systemic manganese homeostasis, we generated mice with single-tissue or two-tissue Zip14 knockout, including intestine-specific (Zip14-In-KO), liver-specific (Zip14-L-KO), and double (intestine and liver) Zip14-knockout (Zip14-DKO) mice. Zip14flox\/flox mice were used as the control. Tissue manganese contents in these mice were compared using inductively coupled plasma mass spectrometry (ICP-MS) analysis. We discovered that although the deletion of intestinal ZIP14 only moderately increased systemic manganese loading, the deletion of both intestinal and hepatic ZIP14 greatly exacerbated the body\u2019s manganese burden. Our results provide new knowledge to further the understanding of manganese metabolism, and offer important insights into the mechanisms underlying systemic manganese overload caused by the loss of ZIP14.<\/jats:p>","DOI":"10.3390\/ijms23126495","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T10:25:12Z","timestamp":1654856712000},"page":"6495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The Combined Inactivation of Intestinal and Hepatic ZIP14 Exacerbates Manganese Overload in Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Caitlin K.","family":"Fung","sequence":"first","affiliation":[{"name":"School of Nutritional Sciences and Wellness, The University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningning","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Nutritional Sciences and Wellness, The University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.2741\/4665","article-title":"Manganese metabolism in humans","volume":"23","author":"Chen","year":"2018","journal-title":"Front. 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