{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:49:00Z","timestamp":1791978540550,"version":"4.4.0"},"reference-count":57,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH NIDDK","award":["DK114478"],"award-info":[{"award-number":["DK114478"]}]},{"DOI":"10.13039\/100012304","name":"School of Medicine, Johns Hopkins University","doi-asserted-by":"crossref","award":["Clinician Scientist Award"],"award-info":[{"award-number":["Clinician Scientist Award"]}],"id":[{"id":"10.13039\/100012304","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"crossref","award":["No. 19-15-00115"],"award-info":[{"award-number":["No. 19-15-00115"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U54AG062333"],"award-info":[{"award-number":["U54AG062333"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,15]]},"abstract":"<jats:p>\n                    ZIP8 is a metal transporter with a role in manganese (Mn) homeostasis. A common genetic variant in ZIP8 (rs13107325; A391T) ranks in the top 10 of pleiotropic SNPs identified in GWAS; A391T has associations with an increased risk of schizophrenia, obesity, Crohn\u2019s disease, and reduced blood Mn. Here, we used CRISPR\/\n                    <jats:italic>Cas9<\/jats:italic>\n                    -mediated knockin (KI) to generate a mouse model of ZIP8 A391T (Zip8 393T-KI mice). Recapitulating the SNP association with blood Mn, blood Mn was reduced in Zip8 393T-KI mice. There was restricted abnormal tissue Mn homeostasis, with decreases in liver and kidney Mn and a reciprocal increase in biliary Mn, providing in vivo evidence of hypomorphic Zip8 function. Upon challenge in a chemically induced colitis model, male Zip8 393T-KI mice exhibited enhanced disease susceptibility. ZIP8 391-Thr associated with reduced triantennary plasma N-glycan species in a population-based cohort to define a genotype-specific glycophenotype hypothesized to be linked to Mn-dependent glycosyltransferase activity. This glycophenotype was maintained in a cohort of patients with Crohn\u2019s disease. These data and the pleiotropic disease associations with ZIP8 391-Thr suggest underappreciated roles of Mn homeostasis in complex human disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.140978","type":"journal-article","created":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T12:01:43Z","timestamp":1599566503000},"source":"Crossref","is-referenced-by-count":66,"title":["Pleiotropic ZIP8 A391T implicates abnormal manganese homeostasis in complex human disease"],"prefix":"10.1172","volume":"5","author":[{"given":"Laxmi","family":"Sunuwar","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azra","family":"Frkatovi\u0107","sequence":"additional","affiliation":[{"name":"Genos Glycoscience Research Laboratory, Zagreb, Croatia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0279-4900","authenticated-orcid":true,"given":"Sodbo","family":"Sharapov","sequence":"additional","affiliation":[{"name":"Laboratory of Glycogenomics, Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2359-3262","authenticated-orcid":true,"given":"Qinchuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"Neu","sequence":"additional","affiliation":[{"name":"University of Maryland School of Pharmacy, University of Maryland, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4661-799X","authenticated-orcid":true,"given":"Xinqun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9005-7750","authenticated-orcid":true,"given":"Talin","family":"Haritunians","sequence":"additional","affiliation":[{"name":"F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyi","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and"},{"name":"Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Michel","sequence":"additional","affiliation":[{"name":"University of Maryland School of Pharmacy, University of Maryland, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoguang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Donowitz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dermot","family":"McGovern","sequence":"additional","affiliation":[{"name":"F. 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