Physiological roles of epidermal sphingolipids with conditional gene targeting.

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Although many scientists predict sphingolipids play important roles in epidermis, its direct evidence is still lacking. To investigate physiological roles of epidermal sphingolipids, we generated a mouse line lacking the first step gene of sphigolipid biosynthesis, SPT, in epidermis. The SPT deficient mice died within 3 weeks after birth. Barrier functions were impaired in the SPT deficient mice. With mass spectrometry analysis sphingolipids bearing three fatty acids were abnormally elevated. These results indicate that de novo synthesis of sphingolipids is important for maintenance of epidermal barrier functions.