The Mask Mutation Identifies TMPRSS6 as an Essential Suppressor of Hepcidin Gene Expression, Required for Normal Uptake of Dietary Iron.

The study identified TMPRSS6 as a crucial suppressor of hepcidin gene expression, necessary for normal dietary iron absorption. The research focused on the Mask mutation, which caused regional alopecia in mice due to iron deficiency. This mutation was linked to a splicing error in the Tmprss6 gene, resulting in a truncated protein lacking the serine protease domain. The study demonstrated that TMPRSS6 down-regulated hepcidin transcription and prevented its upregulation by various stimulators. The findings highlighted TMPRSS6's essential role in the hepcidin suppression pathway, influencing iron metabolism and absorption.