Altered Water Barrier Function in Epidermal-Type Fatty Acid Binding Protein-Deficient Mice

Abstract

We have generated mutant mice for epidermal-type fatty acid binding protein by the gene targeting technique and examined the phenotype in detail. Despite a lack in the expression of epidermal-type fatty acid binding protein mRNA and its protein in the skin and other tissues of the mutant mice, the animals appeared normal in gross and histologic examination. Northern blot analysis of other fatty acid binding proteins revealed a distinct elevated gene expression of heart-type fatty acid binding protein in the skin of the homozygous mice. In analyses of the skin, no differences were observed in contents of major fatty acids, electron microscopic appearance as well as inflammatory responses in ear skin between the mutant and wild-type mice. Basal transepidermal water loss of homozygous mice was lower than that of the wild mice. When acetone was applied to the skin for disruption of the water permeability barrier, recovery in transepidermal water loss was delayed, although maximum transepidermal water loss upon acetone treatment was similar between homozygous and wild-type mice in terms of size and time course. The molecular mechanism by which epidermal-type fatty acid binding protein contributes to the water barrier function of the skin remains to be elucidated.

Thematic review series: Skin Lipids. The role of epidermal lipids in cutaneous permeability barrier homeostasis

“…The amount of E-FABP increases with keratinocyte differentiation, and immunohistochemistry studies have demonstrated that the intensity of staining is greatest in the upper epidermis (96,98,99). The expression of brain, liver, and heart FABP is not usually detected in the epidermis (100,101). Acute disruption of the permeability barrier induces E-FABP expression, and this increase can be prevented by covering with a vapor-permeable membrane (102).…”

“…Additionally, inflammatory disorders, including psoriasis, are associated with increased E-FABP levels in the epidermis (95,97,98). In animals deficient in E-FABP, basal transepidermal water loss is lower than in wild-type animals, (100,101). Of note, though, is that heart FABP is expressed in the epidermis of E-FABP knockout mice (usually not detectable in wild-type mice), and it is possible that this increase in heart FABP compensates for the absence of E-FABP (100, 101).…”

Fatty Acid Binding Protein: Localization and Functional Significance in the Brain

“…However, E-FABP-null mice generated by us are viable, and neither macro-nor microscopic abnormalities have been detected in the brain (Owada et al 2002b). Further studies are necessary to clarify the physiological function of E-FABP in the brain.…”

Reduced size of sebaceous gland and altered sebum lipid composition in mice lacking fatty acid binding protein 5 gene

“…At least 12 members of a genetically related family have been identified, which display distinct patterns of tissue distribution (7). Among the FABP family proteins, FABP5 is expressed in human and murine epidermis and sebaceous glands (8)(9)(10). In the epidermis, FABP5 expression is increased with keratinocyte differentiation, and highly expressed in stratum granulosum where lipid synthesis is active in intercellular lipid production (9-11).…”

“…The generation of FABP5-deficient mice has been described previously (10). Sebaceous glands morphology, immunohistochemical staining and sebaceous lipid composition were evaluated using wild-type and FABP5-deficient mice.…”