title: Compromised epidermal barrier stimulates Harderian gland activity and hypertrophy in ACBP-/- mice.
abstract: Acyl-CoA binding protein (ACBP) is a small, ubiquitously expressed intracellular protein that binds C14-C22 acyl-CoA esters with very high affinity and specificity. We have recently shown that targeted disruption of the Acbp gene leads to a compromised epidermal barrier and that this causes delayed adaptation to weaning, including the induction of the hepatic lipogenic and cholesterogenic gene programs. Here we show that ACBP is highly expressed in the Harderian gland, a gland that is located behind the eyeball of rodents and involved in the production of fur lipids and lipids used for lubrication of the eye lid. We show that disruption of the Acbp gene leads to a significant enlargement of this gland with hypertrophy of the acinar cells and increased de novo synthesis of monoalkyl diacylglycerol, the main lipid species produced by the gland. Mice with conditional targeting of the Acbp gene in the epidermis recapitulate this phenotype, whereas generation of an artificial epidermal barrier during gland development reverses the phenotype. Our findings indicate that the Harderian gland is activated by the compromised epidermal barrier as an adaptive and protective mechanism to overcome the barrier defect.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Signe
authors.initials: S
authors.lastname: Bek
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Ditte
authors.initials: D
authors.lastname: Neess
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Dixen
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Bloksgaard
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Ann-Britt
authors.initials: AB
authors.lastname: Marcher
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: John
authors.initials: J
authors.lastname: Chemnitz
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Nils J
authors.initials: NJ
authors.lastname: Færgeman
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Mandrup
mesh_terms: D061354:Acinar Cells / Q000378:metabolism*; D000818:Animals; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D026261:Diazepam Binding Inhibitor / Q000235:genetics* / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D006243:Harderian Gland / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D050178:Monoglycerides / Q000096:biosynthesis
chemical_list: D026261:Diazepam Binding Inhibitor; D008055:Lipids; D050178:Monoglycerides; D002784:Cholesterol
keywords: acyl-CoA binding protein; impaired epidermal barrier; monoalkyl deacylglycerol synthesis; secretion