title: Sebaceous lipids are essential for water repulsion, protection against UVB-induced apoptosis and ocular integrity in mice.
abstract: Sebocytes, which are characterized by lipid accumulation that leads to cell disruption, can be found in hair follicle-associated sebaceous glands (SGs) or in free SGs such as the Meibomian glands in the eyelids. Because genetic tools that allow targeting of sebocytes while maintaining intact epidermal lipids are lacking, the relevance of sebaceous lipids in health and disease remains poorly understood. Using Scd3, which is expressed exclusively in mature sebocytes, we established a mouse line with sebocyte-specific expression of Cre recombinase. Both RT-PCR analysis and crossing into Rosa26-lacZ reporter mice and Kras(G12D) mice confirmed Cre activity specifically in SGs, with no activity in other skin compartments. Importantly, loss of SCD3 function did not cause detectable phenotypical alterations, endorsing the usefulness of Scd3-Cre mice for further functional studies. Scd3-Cre-induced, diphtheria chain A toxin-mediated depletion of sebaceous lipids resulted in impaired water repulsion and thermoregulation, increased rates of UVB-induced epidermal apoptosis and caused a severe pathology of the ocular surface resembling Meibomian gland dysfunction. This novel mouse line will be useful for further investigating the roles of sebaceous lipids in skin and eye integrity.
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich 81377, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Dahlhoff
authors.affiliation: Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome 00144, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Camera
authors.affiliation: Institute of Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schäfer
authors.affiliation: Institute of Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, Munich 80539, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Emrich
authors.affiliation: School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: Dieter
authors.initials: D
authors.lastname: Riethmacher
authors.affiliation: Centre for Dermatology Research, Institute of Inflammation and Repair, University of Manchester, Manchester M13 9PT, UK.
authors.forename: April
authors.initials: A
authors.lastname: Foster
authors.affiliation: Centre for Dermatology Research, Institute of Inflammation and Repair, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich 81377, Germany marlon.schneider@lmu.de.
authors.forename: Marlon R
authors.initials: MR
authors.lastname: Schneider
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D001833:Body Temperature Regulation / Q000528:radiation effects; D015352:Dry Eye Syndromes / Q000150:complications / Q000473:pathology; D005123:Eye / Q000528:radiation effects*; D006720:Homozygote; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology; D019426:Integrases / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008537:Meibomian Glands / Q000378:metabolism / Q000528:radiation effects; D008810:Mice, Inbred C57BL; D009929:Organ Size; D009928:Organ Specificity / Q000528:radiation effects; D010641:Phenotype; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D012627:Sebaceous Glands / Q000737:chemistry*; D012629:Sebum / Q000378:metabolism; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry*
chemical_list: D008055:Lipids; D014867:Water; C045073:Cre recombinase; D019426:Integrases; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Gene targeting; Meibomian gland disease; Mouse; Sebaceous glands; Water repulsion