Stratum-specific expression of human transferrin receptor increases iron in mouse epidermis

Epidermal desquamation accounts for 20% of the body's iron loss each day. Yet, little is known about how iron content in epidermis is regulated. To test the importance of the transferrin receptor in regulating iron content in epidermis, we created transgenic mice that have stratum-specific expression of the human transferrin receptor. The keratin 14 promoter targeted the receptor primarily to basal, proliferating keratinocytes; the involucrin (Inv) promoter targeted the receptor to suprabasal, differentiating keratinocytes. There were age- and site-dependent differences in iron content in the epidermis and hair. In both types of transgenic mice, epidermal iron content increased with age and at 8 weeks was 2-3-fold greater in transgenic mice compared to littermate controls. Iron was increased up to 2-fold in hair of keratin 14-human transferrin receptor (hTfR) transgenics and 30% in Inv-hTfR transgenics. No gross or histological changes were seen in transgenic animals with increased iron in the epidermis. Ferritin expression, which was low in normal epidermis, was greatly increased in both transgenic lines, indicating that it is the likely depot for the extra iron in these animals. These data show that control of transferrin receptor expression is sufficient to regulate iron content in proliferating or differentiating keratinocytes in the epidermis.