{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:57:30Z","timestamp":1791295050429,"version":"4.1.0"},"reference-count":21,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,4,2]]},"abstract":"<jats:p>\n                    We recently reported the hemochromatosis-like phenotype observed in our\n                    <jats:italic>Usf2<\/jats:italic>\n                    knockout mice. In these mice, as in murine models of hemochromatosis and patients with hereditary hemochromatosis, iron accumulates in parenchymal cells (in particular, liver and pancreas), whereas the reticuloendothelial system is spared from this iron loading. We suggested that this phenotypic trait could be attributed to the absence, in the\n                    <jats:italic>Usf2<\/jats:italic>\n                    knockout mice, of a secreted liver-specific peptide, hepcidin. We conjectured that the reverse situation, namely overexpression of hepcidin, might result in phenotypic traits of iron deficiency. This question was addressed by generating transgenic mice expressing hepcidin under the control of the liver-specific transthyretin promoter. We found that the majority of the transgenic mice were born with a pale skin and died within a few hours after birth. These transgenic animals had decreased body iron levels and presented severe microcytic hypochromic anemia. So far, three mosaic transgenic animals have survived. They were unequivocally identified by physical features, including reduced body size, pallor, hairless and crumpled skin. These pleiotropic effects were found to be associated with erythrocyte abnormalities, with marked anisocytosis, poikylocytosis and hypochromia, which are features characteristic of iron-deficiency anemia. These results strongly support the proposed role of hepcidin as a putative iron-regulatory hormone. The animal models devoid of hepcidin (the\n                    <jats:italic>Usf2<\/jats:italic>\n                    knockout mice) or overexpressing the peptide (the transgenic mice presented in this paper) represent valuable tools for investigating iron homeostasis\n                    <jats:italic>in vivo<\/jats:italic>\n                    and for deciphering the molecular mechanisms of hepcidin action.\n                  <\/jats:p>","DOI":"10.1073\/pnas.072632499","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"4596-4601","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":682,"title":["Severe iron deficiency anemia in transgenic mice expressing liver hepcidin"],"prefix":"10.1073","volume":"99","author":[{"given":"Ga\u00ebl","family":"Nicolas","sequence":"first","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique, d\u00e9veloppement et Pathologie Mol\u00e9culaire, Institut Cochin, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, et Universit\u00e9 Ren\u00e9 Descartes, Facult\u00e9 de M\u00e9decine Cochin-Port Royal, 75014 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale 409, Facult\u00e9 de M\u00e9decine Xavier Bichat, 75018 Paris, France; and Department of Molecular Genetics, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Bennoun","sequence":"additional","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique, d\u00e9veloppement et Pathologie Mol\u00e9culaire, Institut Cochin, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, et Universit\u00e9 Ren\u00e9 Descartes, Facult\u00e9 de M\u00e9decine Cochin-Port Royal, 75014 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale 409, Facult\u00e9 de M\u00e9decine Xavier Bichat, 75018 Paris, France; and Department of Molecular Genetics, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlette","family":"Porteu","sequence":"additional","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique, d\u00e9veloppement et Pathologie Mol\u00e9culaire, Institut Cochin, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, et Universit\u00e9 Ren\u00e9 Descartes, Facult\u00e9 de M\u00e9decine Cochin-Port Royal, 75014 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale 409, Facult\u00e9 de M\u00e9decine Xavier Bichat, 75018 Paris, France; and Department of Molecular Genetics, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Mativet","sequence":"additional","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique, d\u00e9veloppement et Pathologie Mol\u00e9culaire, Institut Cochin, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, et Universit\u00e9 Ren\u00e9 Descartes, Facult\u00e9 de M\u00e9decine Cochin-Port Royal, 75014 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale 409, Facult\u00e9 de M\u00e9decine Xavier Bichat, 75018 Paris, France; and Department of Molecular Genetics, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Beaumont","sequence":"additional","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique, d\u00e9veloppement et Pathologie Mol\u00e9culaire, Institut Cochin, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, et Universit\u00e9 Ren\u00e9 Descartes, Facult\u00e9 de M\u00e9decine Cochin-Port Royal, 75014 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale 409, Facult\u00e9 de M\u00e9decine Xavier Bichat, 75018 Paris, France; and Department of Molecular Genetics, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Grandchamp","sequence":"additional","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique, d\u00e9veloppement et Pathologie Mol\u00e9culaire, Institut Cochin, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, et Universit\u00e9 Ren\u00e9 Descartes, Facult\u00e9 de M\u00e9decine Cochin-Port Royal, 75014 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale 409, Facult\u00e9 de M\u00e9decine Xavier Bichat, 75018 Paris, France; and Department of Molecular Genetics, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Sirito","sequence":"additional","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique, d\u00e9veloppement et Pathologie Mol\u00e9culaire, Institut Cochin, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, et Universit\u00e9 Ren\u00e9 Descartes, Facult\u00e9 de M\u00e9decine Cochin-Port Royal, 75014 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale 409, Facult\u00e9 de M\u00e9decine Xavier Bichat, 75018 Paris, France; and Department of Molecular Genetics, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mich\u00e8le","family":"Sawadogo","sequence":"additional","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique, d\u00e9veloppement et Pathologie Mol\u00e9culaire, Institut Cochin, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, et Universit\u00e9 Ren\u00e9 Descartes, Facult\u00e9 de M\u00e9decine Cochin-Port Royal, 75014 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale 409, Facult\u00e9 de M\u00e9decine Xavier Bichat, 75018 Paris, France; and Department of Molecular Genetics, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Kahn","sequence":"additional","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique, d\u00e9veloppement et Pathologie Mol\u00e9culaire, Institut Cochin, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, et Universit\u00e9 Ren\u00e9 Descartes, Facult\u00e9 de M\u00e9decine Cochin-Port Royal, 75014 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale 409, Facult\u00e9 de M\u00e9decine Xavier Bichat, 75018 Paris, France; and Department of Molecular Genetics, University of Texas, M. D. 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Anderson Cancer Center, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,4,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/35042073"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.108.4.960"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.13.4020.h8004020_4020_4027"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151179498"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008922200"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01920-7"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008923200"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0896-399"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.5.2492"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3758"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.35.21944"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)85167-0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1990.tb08184.x"},{"key":"e_1_3_3_14_2","first-page":"90","volume":"1","author":"Torrance J D","year":"1980","unstructured":"J D Torrance, T H Bothwell Methods Hematol 1, 90\u2013115 (1980).","journal-title":"Methods Hematol"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.116.3.783"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/7727"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.24.13198"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0897-383"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/35001596"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80425-6"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.161296298"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.072632499","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T16:53:15Z","timestamp":1649782395000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.072632499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,4,2]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2002,4,2]]}},"alternative-id":["10.1073\/pnas.072632499"],"URL":"https:\/\/doi.org\/10.1073\/pnas.072632499","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,4,2]]},"assertion":[{"value":"2001-11-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-04-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}