Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter

Defects in iron absorption and utilization lead to iron deficiency and over load disorders. Adult mammals absorb iron through the duodenum, whereas emb ryos obtain iron through placental transport. Iron uptake from the intestin al lumen through the apical surface of polarized duodenal enterocytes is me diated by the divalent metal transporter, DMT1 (refs 1-3). A second transpo rter has been postulated to export iron across the basolateral surface to t he circulation. Here we have used positional cloning to identify the gene r esponsible for the hypochromic anaemia of the zebrafish mutant weissherbst. The gene, ferroportin1, encodes a multiple-transmembrane domain protein, e xpressed in the yolk sac, that is a candidate for the elusive iron exporter . Zebrafish ferroportin1 is required for the transport of iron from materna lly derived yolk stores to the circulation and functions as an iron exporte r when expressed in Xenopus oocytes. Human Ferroportin1 is found at the bas al surface of placental syncytiotrophoblasts, suggesting that it also trans ports iron from mother to embryo. Mammalian Ferroportin1 is expressed at th e basolateral surface of duodenal enterocytes and could export cellular iro n into the circulation. We propose that Ferroportin1 function may be pertur bed in mammalian disorders of iron deficiency or overload.