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.

Neuroendocrinology and neurobiology of sebaceous glands

“…MC5R is also present in murine SGs (Chen et al ., ; Thiboutot et al ., ). Mice that are genetically deficient for Mc5r demonstrate impaired temperature homeostasis and a reduced ability to shed water from their fur, similar to other sebaceous lipid‐deficient mice (Chen et al ., ; Sampath et al ., ; Dahlhoff et al ., ). Importantly, Mc5r –/– mice exhibit a 15–20% reduction in sebum production (Chen et al ., ).…”

“…Evidence from the cutaneous phenotypes present in mice that are deficient for sebaceous lipids (Ehrmann & Schneider, ) highlight the important functions of sebum in skin physiology. These functions include: waterproofing of skin and fur (Chen et al ., ; Chen et al ., ; Westerberg et al ., ; Dahlhoff et al ., ), anti‐microbial activity (Basta, Wilburg & Heczko, ; Wille & Kydonieus, ; Drake et al ., ; Lee et al ., ; Nakatsuji et al ., ), maintenance of skin barrier function (Sundberg et al ., ; Fluhr et al ., ; Westerberg et al ., ; Man et al ., ), protection against ultraviolet radiation (Beadle & Burton, ; Ohsawa et al ., ; Passi et al ., ; Mudiyanselage et al ., ; Ryu et al ., ; Dahlhoff et al ., ), and regulation of body temperature (Chen et al ., ; Chen et al ., ; Sampath et al ., ; Dahlhoff et al ., ).…”

Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

“…There is also now evidence indicating that the SG serves important physiological roles, indicated by mouse models that lack SGs and sebaceous lipids . For example, mice that are genetically deficient for differentiated sebocytes exhibit impaired waterproofing of fur, are unable to regulate body temperature properly, and are more susceptible to ultraviolet radiation‐induced apoptosis in the epidermis and HFs . Sebum may also be required for maintaining skin barrier function, and loss of SGs is frequently associated with scarring alopecia in mice, suggesting a role of SGs in HF maintenance.…”

“…22 For example, mice that are genetically deficient for differentiated sebocytes exhibit impaired waterproofing of fur, are unable to regulate body temperature properly, and are more susceptible to ultraviolet radiation-induced apoptosis in the epidermis and HFs. 23 Sebum may also be required for maintaining skin barrier function, and loss of SGs is frequently associated with scarring alopecia in mice, [24][25][26] suggesting a role of SGs in HF maintenance. Furthermore, sebocytes have an immunomodulatory capacity 27,28 and can produce several lipids and peptides that have demonstrable antimicrobial properties.…”

Cicatricial Alopecia Research Foundation meeting, May 2016: Progress towards the diagnosis, treatment and cure of primary cicatricial alopecias

“…However, not all mutated genes that are normally expressed in the sebaceous gland cause these diseases . For example, mice with mutations in Soat1, melanocortin 5 receptor ( Mc5r e ) and stearoyl‐coenzyme A desaturase 3 ( Scd3 ) do not exhibit follicular scarring, yet all these genes are expressed in the sebaceous gland. These results indicate that abnormalities in sebceous glands and/or their secretions alone will not be sufficient to develop PCA.…”