{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:14:00Z","timestamp":1787004840610,"version":"build-2736575974"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T00:00:00Z","timestamp":1033430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2003,12,30]],"date-time":"2003-12-30T00:00:00Z","timestamp":1072742400000},"content-version":"vor","delay-in-days":455,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["DK20503"],"award-info":[{"award-number":["DK20503"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,10]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Several methods have been used to develop rodent models with the hepatic manifestations of porphyria cutanea tarda (PCT). Acute iron administration or mutations of the hemochromatosis gene (\n                      <jats:italic toggle=\"yes\">Hfe<\/jats:italic>\n                      ) have been used to generate hepatic siderosis, a nearly uniform finding in PCT. Heterozygosity for a null mutation at the uroporphyrinogen decarboxylase (\n                      <jats:italic toggle=\"yes\">Uro-D<\/jats:italic>\n                      +\/\u2212) locus has been developed to mimic familial PCT in humans. This study examines the interplay of these 2 genetic risk factors and their influence, alone and combined with polychlorinated-biphenyl exposure. Neither an\n                      <jats:italic toggle=\"yes\">Hfe<\/jats:italic>\n                      -null mutation nor iron-dextran administration alone or in combination with polychlorinated biphenyl exposure was porphyrinogenic in a 3-week model using mice wild-type at the\n                      <jats:italic toggle=\"yes\">Uro-D<\/jats:italic>\n                      locus. Homozygosity for an\n                      <jats:italic toggle=\"yes\">Hfe<\/jats:italic>\n                      -null mutation significantly elevated hepatic iron but not to the extent seen with parenteral iron-dextran administration. Homozygosity for an\n                      <jats:italic toggle=\"yes\">Hfe<\/jats:italic>\n                      -null mutation but not iron-dextran administration was porphyrinogenic in animals heterozygous for the\n                      <jats:italic toggle=\"yes\">Uro-D<\/jats:italic>\n                      mutation. Polychlorinated biphenyls were also porphyrinogenic in these animals. Uroporphyria in\n                      <jats:italic toggle=\"yes\">Uro-D<\/jats:italic>\n                      +\/\u2212 animals was exacerbated by combinations of the homozygous\n                      <jats:italic toggle=\"yes\">Hfe<\/jats:italic>\n                      -null mutation and polychlorinated biphenyls and iron-dextran and polychlorinated biphenyls. In all cases in which uroporphyria developed, a greater degree of experimental uroporphyria was seen in female animals. All elevated hepatic uroporphyrin concentrations were accompanied by depressed uroporphyrinogen decarboxylase activity and the presence of a factor in cytosol that inhibits recombinant human uroporphyrinogen decarboxylase. In conclusion, the expression of the uroporphyric phenotype, dependent on the susceptibility imparted by a genetic mutation, provides a uniquely facile model for dissecting the molecular pathogenesis of the disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1053\/jhep.2002.35621","type":"journal-article","created":{"date-parts":[[2003,3,25]],"date-time":"2003-03-25T21:15:53Z","timestamp":1048626953000},"page":"805-811","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Uroporphyria in the uroporphyrinogen decarboxylase-deficient mouse: Interplay with siderosis and polychlorinated biphenyl exposure"],"prefix":"10.1097","volume":"36","author":[{"given":"Michael R.","family":"Franklin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John 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