Increased expression of aquaporin-3 in the epidermis of DHCR24 knockout mice

Background The DHCR24 (3 beta-hydroxysterol-Delta 24 reductase) gene encodes an enzyme catalysing conversion of desmosterol to cholesterol. Desmosterolosis is an autosomal recessive disease due to mutation in the DHCR24 gene, with low cholesterol and high desmosterol levels. To understand the pathophysiology of this disease, we utilized DHCR24 knockout mice and reported that DHCR24-/- mice die soon after birth. Their skin was less wrinkled, shiny, and revealed features of lethal restrictive dermopathy associated with severe defects in epidermal maturation and barrier function. Objectives Markedly increased transepidermal water loss in DHCR24-/- mice led us to examine the role of aquaporin-3 (AQP3), because this is the only water/glycerol transporting channel protein expressed in the epidermis. Methods Expression of AQP3 was studied by Western blot analysis and immunohistochemistry in the epidermis of DHCR24-/- and wild-type newborn mice. Glycerol uptake was determined in the isolated keratinocytes and glycerol content in the epidermis was analysed by an enzymatic method. Results In control mice, AQP3 was expressed only in cells of the stratum basale, indicating its expression in immature keratinocytes. In DHCR24-/- mice, AQP3 was expressed throughout the epidermis and colocalized with the immature keratinocytes (keratin 14-positive cells). The increased AQP3 expression in the epidermis of DHCR24-/- mice was mirrored by a significantly higher glycerol uptake and glycerol content. This was associated with an increase in epidermal water content of DHCR24-/- mice. Conclution This is the first demonstration that elevated AQP3 results in the retention of epidermal water, causing the taut, wrinkle-free skin phenotype of the DHCR24-/- mice.