title: The acyl-CoA binding protein is required for normal epidermal barrier function in mice.
abstract: 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.
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark; MEMPHYS-Center for Biomembrane Physics, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Maria
authors: M
authors: Bloksgaard
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Signe
authors: S
authors: Bek
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Ann-Britt
authors: AB
authors: Marcher
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Ditte
authors: D
authors: Neess
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark; MEMPHYS-Center for Biomembrane Physics, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Jonathan
authors: J
authors: Brewer
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Hans Kristian
authors: HK
authors: Hannibal-Bach
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Torben
authors: T
authors: Helledie
authors: Institute of Molecular Medicine, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Christina
authors: C
authors: Fenger
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Marianne
authors: M
authors: Due
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Zane
authors: Z
authors: Berzina
authors: Institut für Pharmazie, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany.
authors: Reinhard
authors: R
authors: Neubert
authors: Institute of Molecular Medicine, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: John
authors: J
authors: Chemnitz
authors: Institute of Molecular Medicine, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Bente
authors: B
authors: Finsen
authors: Department of Dermatology, Odense University Hospital, Odense, Denmark; and.
authors: Anders
authors: A
authors: Clemmensen
authors: Department of Dermatology, Karolinska Center of Transgene Technologies, Stockholm, Sweden.
authors: Johannes
authors: J
authors: Wilbertz
authors: Laboratory Animal Science and Comparative Medicine, University of Southern Denmark, DK-5230 Odense, Denmark and.
authors: Henrik
authors: H
authors: Saxtorph
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Jens
authors: J
authors: Knudsen
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark; MEMPHYS-Center for Biomembrane Physics, University of Southern Denmark, DK-5230 Odense, Denmark; Danish Molecular Biomedical Imaging Center (DaMBIC), University of Southern Denmark, DK-5230 Odense, Denmark. Electronic address: bagatolli@memphys.sdu.dk.
authors: Luis
authors: L
authors: Bagatolli
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark. Electronic address: s.mandrup@bmb.sdu.dk.
authors: Susanne
authors: S
authors: Mandrup
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D026261:Diazepam Binding Inhibitor / Q000235:genetics* / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D013058:Mass Spectrometry; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D012627:Sebaceous Glands / Q000737:chemistry / Q000378:metabolism; D012867:Skin / Q000737:chemistry / Q000378:metabolism
chemical_list: D026261:Diazepam Binding Inhibitor; D008055:Lipids; D002784:Cholesterol