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The serine protease TMPRSS6 is required to sense iron deficiency.

Science (New York, N.Y.) | May 23, 2008

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.

Pubmed ID: 18451267 RIS Download

Mesh terms: Anemia, Macrocytic | Animals | Antimicrobial Cationic Peptides | Cell Line, Tumor | Gene Expression Regulation | Hepcidins | Humans | Iron | Membrane Proteins | Mice | Mice, Mutant Strains | Mice, Transgenic | Models, Biological | Mutation | Phenotype | Promoter Regions, Genetic | Protein Structure, Tertiary | Serine Endopeptidases | Signal Transduction | Transfection

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Associated grants

  • Agency: NIDDK NIH HHS, Id: R01 DK053505-09
  • Agency: NIAID NIH HHS, Id: U54 AI054523-019005
  • Agency: NIAID NIH HHS, Id: AI054523
  • Agency: NIDDK NIH HHS, Id: DK53505-09
  • Agency: NIAID NIH HHS, Id: U54 AI054523

Mouse Genome Informatics (Data, Gene Annotation)

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