title: Ceramide synthase 4 deficiency in mice causes lipid alterations in sebum and results in alopecia.
abstract: Five ceramide synthases (CerS2-CerS6) are expressed in mouse skin. Although CerS3 has been shown to fulfill an essential function during skin development, neither CerS6- nor CerS2-deficient mice show an obvious skin phenotype. In order to study the role of CerS4, we generated CerS4-deficient mice (Cers4-/-) and CerS4-specific antibodies. With these biological tools we analysed the tissue distribution and determined the cell-type specific expression of CerS4 in suprabasal epidermal layers of footpads as well as in sebaceous glands of the dorsal skin. Loss of CerS4 protein leads to an altered lipid composition of the sebum, which is more solidified and therefore might cause progressive hair loss due to physical blocking of the hair canal. We also noticed a strong decrease in C20 1,2-alkane diols consistent with the decrease of wax diesters in the sebum of Cers4-/- mice. Cers4-/- mice at 12 months old display additional epidermal tissue destruction due to dilated and obstructed pilary canals. Mass spectrometric analyses additionally show a strong decrease in C20-containing sphingolipids.
authors.affiliation: *Molecular Genetics, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Ebel
authors.affiliation: *Molecular Genetics, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Imgrund
authors.affiliation: †Institute of Molecular Physiology and Biotechnology of Plants, University of Bonn, 53115 Bonn, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Vom Dorp
authors.affiliation: *Molecular Genetics, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Hofmann
authors.affiliation: ‡Institute of Biochemistry and Molecular Biology, University of Bonn, 53115 Bonn, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Maier
authors.affiliation: *Molecular Genetics, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Drake
authors.affiliation: *Molecular Genetics, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Degen
authors.affiliation: †Institute of Molecular Physiology and Biotechnology of Plants, University of Bonn, 53115 Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Dörmann
authors.affiliation: ‡Institute of Biochemistry and Molecular Biology, University of Bonn, 53115 Bonn, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eckhardt
authors.affiliation: §Institute of Anatomy, University of Bonn, 53115 Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Franz
authors.affiliation: *Molecular Genetics, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
mesh_terms: D000505:Alopecia / Q000201:enzymology* / Q000209:etiology* / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D018450:Disease Progression; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000172:deficiency* / Q000235:genetics; D012629:Sebum / Q000201:enzymology*; D013107:Sphingolipids / Q000009:adverse effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D013107:Sphingolipids; D010088:Oxidoreductases; C108138:dihydroceramide desaturase