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Series GSE135643 Query DataSets for GSE135643
Status Public on Nov 07, 2019
Title SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation
Organism Mus musculus
Experiment type Expression profiling by array
Summary SDR9C7 encodes an orphan short-chain dehydrogenase/reductase recently found mutated in ichthyosis. In a patient with SDR9C7 mutation and a mouse Sdr9c7 knockout model we show loss of covalent binding of epidermal ceramides to protein, a structural fault in the barrier. For reasons unresolved, protein binding requires lipoxygenase-catalyzed transformations of linoleic acid (18:2) esterified in ω-O-acylceramides. In Sdr9c7-/- epidermis, quantitative LC-MS assays revealed almost complete loss of a species of ω-O-acylceramide esterified with linoleate-9,10-trans-epoxy-11E-13-ketone; other acylceramides related to the lipoxygenase pathway were in higher abundance. Recombinant SDR9C7 catalyzed NAD-dependent dehydrogenation of linoleate 9,10-trans-epoxy-11E-13-alcohol to the corresponding 13-ketone, while ichthyosis mutants were inactive. We propose, therefore, that the critical requirement for lipoxygenases and SDR9C7 is in producing acylceramide containing the 9,10-epoxy-11E-13-ketone, a reactive moiety known for its non-enzymatic coupling to protein. This suggests a novel mechanism for coupling of ceramide to protein and provides important insights into skin barrier formation and pathogenesis.
Overall design We compared gene expression in Sdr9c7-/- (knockout) epidermis at P0 with Sdr9c7+/+ (wild type) controls. Individual array samples were generated by pooling equal amounts of total RNA derived from skins of 5 animals.
Contributor(s) Hirabayashi T, Nishito Y, Takeichi T, Akiyama M
Citation(s) 31671075
Submission date Aug 09, 2019
Last update date Feb 06, 2020
Contact name Tetsuya Hirabayashi
Organization name Tokyo Metropolitan Institute of Medical Science
Lab Biomembrane
Street address 2-1-6 Kamikitazawa, Setagaya-ku
City Tokyo
ZIP/Postal code 156-8506
Country Japan
Platforms (1)
GPL10333 Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Feature Number version)
Samples (2)
GSM4025384 Skin_Sdr9c7_WT_P0
GSM4025385 Skin_Sdr9c7_KO_P0
BioProject PRJNA559537

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Supplementary file Size Download File type/resource
GSE135643_RAW.tar 24.3 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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