Expression of the keratinocyte lipid transporter ABCA12 in developing and reconstituted human epidermis

Serious defects in the epidermal keratinocyte lipid transporter ABCA12 are known to result in a deficient skin lipid barrier, leading to harlequin ichthyosis (HI). HI is the most severe inherited keratinizing disorder and is frequently fatal in the perinatal period. To clarify the role of ABCA12, ABCA12 expression was studied in developing human skin and HI lesions artificially reconstituted in immunodeficient mice. By immunofluorescent study, ABCA12 was expressed in the periderm of the early stage two-layered human fetal epidermis. After formation of a three-layered epidermis, ABCA12 staining was seen throughout the entire epidermis. ABCA12 mRNA expression significantly increased during human skin development and reached 62% of the expression in normal adult skin, whereas the expression rate of transglutaminase 1, loricrin, and kallikrein 7 remained low. We transplanted keratinocytes from patients with HI and succeeded in reconstituting HI skin lesions in immunodeficient mice. The reconstituted lesions showed similar changes to those of patients with HI. Our findings demonstrate that ABCA12 is highly expressed in fetal skin and suggest that ABCA12 may play an essential role under both the wet and dry conditions, including the dramatic turning point from a wet environment of the amniotic fluid to a dry environment after birth.