{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:19:44Z","timestamp":1790813984941,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T00:00:00Z","timestamp":1581033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006400","name":"Alnylam Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006400","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Reduced ferrochelatase activity in erythropoietic protoporphyria (EPP) causes the accumulation of protoporphyrin IX (PPIX) leading to acute cutaneous photosensitivity and liver injury. Many EPP patients also have a mild hypochromic, microcytic anemia and iron deficiency. Iron deficiency can lead to decreased PPIX accumulation in another erythropoietic porphyria, congenital erythropoietic porphyria (CEP). Expression of the iron regulatory peptide hepcidin is negatively regulated by the serine protease<jats:italic>TMPRSS6<\/jats:italic>. Hepcidin induction by siRNA\u2010mediated inhibition of<jats:italic>TMPRSS6<\/jats:italic>expression reduces iron availability and induces iron deficiency. To interrogate the therapeutic potential of iron deficiency to modify EPP, we treated an ethylnitrosourea\u2010induced mouse model of EPP,<jats:italic>Fech<\/jats:italic><jats:sup><jats:italic>m1Pas<\/jats:italic><\/jats:sup>, with a GalNAc<jats:italic>\u2010<\/jats:italic>conjugated<jats:italic>Tmprss6<\/jats:italic>siRNA and PPIX levels, anemia and iron parameters were monitored. The GalNAc\u2010RNAi therapeutic reduces<jats:italic>Tmprss6<\/jats:italic>expression and induces mild iron deficiency in<jats:italic>Fech<\/jats:italic><jats:sup><jats:italic>m1Pas<\/jats:italic><\/jats:sup>animals. However, decreases in erythrocyte PPIX levels and liver PPIX accumulation were not seen. These results indicate short\u2010term induction of iron deficiency, at least in a murine model of EPP, does not lead to decreased PPIX production.<\/jats:p>","DOI":"10.1002\/ajh.25743","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T15:09:51Z","timestamp":1580224191000},"page":"492-496","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Mild iron deficiency does not ameliorate the phenotype of a murine erythropoietic protoporphyria model"],"prefix":"10.1002","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6978-0656","authenticated-orcid":false,"given":"Paul J.","family":"Schmidt","sequence":"first","affiliation":[{"name":"Department of Pathology Boston Children's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica L.","family":"Hollowell","sequence":"additional","affiliation":[{"name":"Department of Pathology Boston Children's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Alnylam Pharmaceuticals, Inc. 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