Genetically modified laboratory mice with sebaceous glands abnormalities

Abstract

Sebaceous glands (SG) are exocrine glands that release their product by holocrine secretion, meaning that the whole cell becomes a secretion following disruption of the membrane. SG may be found in association with a hair follicle, forming the pilosebaceous unit, or as modified SG at different body sites such as the eyelids (Meibomian glands) or the preputial glands. Depending on their location, SG fulfill a number of functions, including protection of the skin and fur, thermoregulation, formation of the tear lipid film, and pheromone-based communication. Accordingly, SG abnormalities are associated with several diseases such as acne, cicatricial alopecia, and dry eye disease. An increasing number of genetically modified laboratory mouse lines develop SG abnormalities, and their study may provide important clues regarding the molecular pathways regulating SG development, physiology, and pathology. Here, we summarize in tabulated form the available mouse lines with SG abnormalities and, focusing on selected examples, discuss the insights they provide into SG biology and pathology. We hope this survey will become a helpful information source for researchers with a primary interest in SG but also as for researchers from unrelated fields that are unexpectedly confronted with a SG phenotype in newly generated mouse lines.

Inactivation of autophagy leads to changes in sebaceous gland morphology and function

“…Site‐specific differences in the morphology of SG and hair size and form as well as epidermal thickness are well established. To ascertain whether such site‐specific effects had been described in other reports, we searched for studies of mouse mutations which have affected SG size . This revealed that most laboratories restrict their observations to either tail or back skin.…”

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 .…”

“…There is also now evidence indicating that the SG serves important physiological roles, indicated by mouse models that lack SGs and sebaceous lipids. 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.…”

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

“…A number of additional mouse models have been identified naturally or created by genetic engineering with similar sequelae (Table ). 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.…”