The serine protease TMPRSS6 is required to sense iron deficiency

Xin Du, Ellen She, Terri Gelbart, Jaroslav Truksa, Pauline Lee, Yu Xia, Kevin Khovananth, Suzanne Mudd, Navjiwan Mann, Eva Marie Y Moresco, Ernest Beutler, Bruce Beutler

Research output: Contribution to journalArticle

413 Scopus citations

Abstract

Hepcidin, a liver-derived protein that restricts enteric iron absorption, is the key regulator of body iron content. Several proteins induce expression of the hepcidin-encoding gene Hamp in response to infection or high levels of iron. However, mechanism(s) of Hamp suppression during iron depletion are poorly understood. We describe mask: a recessive, chemically induced mutant mouse phenotype, characterized by progressive loss of body (but not facial) hair and microcytic anemia. The mask phenotype results from reduced absorption of dietary iron caused by high levels of hepcidin and is due to a splicing defect in the transmembrane serine protease 6 gene Tmprss6. Overexpression of normal TMPRSS6 protein suppresses activation of the Hamp promoter, and the TMPRSS6 cytoplasmic domain mediates Hamp suppression via proximal promoter element(s). TMPRSS6 is an essential component of a pathway that detects iron deficiency and blocks Hamp transcription, permitting enhanced dietary iron absorption.

Original languageEnglish (US)
Pages (from-to)1088-1092
Number of pages5
JournalScience
Volume320
Issue number5879
DOIs
StatePublished - May 23 2008

ASJC Scopus subject areas

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    Du, X., She, E., Gelbart, T., Truksa, J., Lee, P., Xia, Y., Khovananth, K., Mudd, S., Mann, N., Moresco, E. M. Y., Beutler, E., & Beutler, B. (2008). The serine protease TMPRSS6 is required to sense iron deficiency. Science, 320(5879), 1088-1092. https://doi.org/10.1126/science.1157121