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Unmasking the Sensor of Iron Deficiency

Iron homeostasis is important because most animals require it and high levels can be toxic. Despite being a relatively common metabolic condition, very little is known about how iron deficiency is perceived in mammals. Mouse mask mutants are characterized by iron deficiency anemia and loss of body hair. The chemically induced mutation in the mask strain was positionally cloned by Du et al. and found to map to the transmembrane serine protease 6 (Tmprss6), where it interferes with splicing. Overexpression of Tmprss6 caused transcriptional repression of the Hamp gene, which encodes the peptide hormone hepcidin. Hepcidin represses iron absorption by intestinal cells. The authors conclude that Tmprss6 is part of the iron-sensing machinery that relays an iron deficiency signal to the molecules that control dietary absorption. X. Du, E. She, T. Gelbart, J. Truksa, P. Lee, Y. Xia, K. Khovananth, S. Mudd, N. Mann, E. M. Y. Moresco, E. Beutler, B. Beutler, The serine protease TMPRSS6 is required to sense iron deficiency. Science 320, 1088-1092 (2008). [Abstract] [Full Text]