Disruption of ferroportin 1 regulation causes dynamic alterations in iron homeostasis and erythropoiesis in polycythaemia mice

• DOI: 10.1242/dev.01081
• Publication Date: 2004-03-30T22:33:04Z
• Authors: Henry Mok; Jaroslav Jelinek; Sonia Pai; Bruce M. Cattanach; Josef T. Prchal; Hagop Youssoufian; Armin Schumacher
• Keywords: Ferroportin; HAMP; Homeostasis; Ineffective erythropoiesis

Coding region mutations in the principal basolateral iron transporter of duodenal enterocyte, ferroportin 1 (FPN1), lead to autosomal dominant reticuloendothelial overload humans. We report positional cloning a hypermorphic, regulatory mutation Fpn1 from radiation-induced polycythaemia (Pcm) mice. A 58 bp microdeletion Fpn1promoter alters transcription start sites and eliminates responsive element (IRE) 5′ untranslated region, resulting increased hepatic protein levels during early postnatal development. Pcm mutants, which are deficient at birth,exhibited Fpn1-mediated uptake as young adult Additionally, mutants displayed an erythropoietin (Epo)-dependent polycythemia heterozygotes hypochromic, microcytic anemia homozygotes. Interestingly, both defects erythropoiesis were transient, correcting by adulthood. Delayed upregulation negative hormonal regulator homeostasis, hepcidin(Hamp), development correlates strongly with profound increases Pcmheterozygotes. Thus, our data suggest that Hamp-mediated interference alleviates homeostasis transient alterations caused Fpn1.