TY - JOUR
T1 - The serine protease TMPRSS6 is required to sense iron deficiency
AU - Du, Xin
AU - She, Ellen
AU - Gelbart, Terri
AU - Truksa, Jaroslav
AU - Lee, Pauline
AU - Xia, Yu
AU - Khovananth, Kevin
AU - Mudd, Suzanne
AU - Mann, Navjiwan
AU - Moresco, Eva Marie Y
AU - Beutler, Ernest
AU - Beutler, Bruce
PY - 2008/5/23
Y1 - 2008/5/23
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1157121
DO - 10.1126/science.1157121
M3 - Article
C2 - 18451267
AN - SCOPUS:44449177930
SN - 0036-8075
VL - 320
SP - 1088
EP - 1092
JO - Science
JF - Science
IS - 5879
ER -