The acyl-CoA binding protein is required for normal epidermal barrier function in mice

Maria Bloksgaard, Signe Bek, Ann-Britt Marcher, Ditte Neess, Jonathan Brewer, Hans Kristian Hannibal-Bach, Torben Helledie, Christina Fenger, Marianne Due, Zane Berzina, Reinhard Neubert, John Chemnitz, Bente Finsen, Anders Clemmensen, Johannes Wilbertz, Henrik Saxtorph, Jens Knudsen, Luis Bagatolli, Susanne Mandrup

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The acyl-CoA binding protein (ACBP) is a 10 kDa intracellular protein expressed in all eukaryotic species. Mice with targeted disruption of Acbp (ACBP(-/-) mice) are viable and fertile but present a visible skin and fur phenotype characterized by greasy fur and development of alopecia and scaling with age. Morphology and development of skin and appendages are normal in ACBP(-/-) mice; however, the stratum corneum display altered biophysical properties with reduced proton activity and decreased water content. Mass spectrometry analyses of lipids from epidermis and stratum corneum of ACBP(+/+) and ACBP(-/-) mice showed very similar composition, except for a significant and specific decrease in the very long chain free fatty acids (VLC-FFA) in stratum corneum of ACBP(-/-) mice. This finding indicates that ACBP is critically involved in the processes that lead to production of stratum corneum VLC-FFAs via complex phospholipids in the lamellar bodies. Importantly, we show that ACBP(-/-) mice display a ∼50% increased transepidermal water loss compared with ACBP(+/+) mice. Furthermore, skin and fur sebum monoalkyl diacylglycerol (MADAG) levels are significantly increased, suggesting that ACBP limits MADAG synthesis in sebaceous glands. In summary, our study shows that ACBP is required for production of VLC-FFA for stratum corneum and for maintaining normal epidermal barrier function.
TidsskriftJournal of Lipid Research
Udgave nummer10
Sider (fra-til)2162-74
Antal sider13
StatusUdgivet - 2012


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