Fifty years of the asebia mouse: origins, insights and contemporary developments

Abstract

First described as an alopecic spontaneous mutant mouse line lacking sebaceous glands in a publication in Science in 1965 by Allen H. Gates and Marvin Karasek, asebia mice soon became a popular tool for rodent sebaceous gland research. In addition to the study of sebaceous lipids, the original asebia mice and subsequent allelic mutations were widely employed to examine the influence of the sebaceous gland on hair growth, epidermal proliferation, dermal inflammation and skin carcinogenesis, among other aspects. With the identification of Scd1 gene mutations as the genetic basis of the asebia phenotype and with the advent of more refined methods for manipulating the mouse genome, asebia mice progressively lost importance. However, they contributed to, or even provided the initial spark for, several current research topics. These include the role of the sebaceous gland in hair shaft-sheath interaction and its significance for cicatricial alopecia, and the antimicrobial activity of sebum. Furthermore, mice with skin-specific deletion of SCD1, which have increased energy expenditure and are protected from high fat diet-induced obesity, provided novel insights into the crosstalk between the skin and peripheral tissues in maintaining energy homeostasis. In briefly reviewing its story, this commentary pays tribute to asebia mice and to the original publication in its golden anniversary year.

Getting to the root of scales, feather and hair: As deep as odontodes?

“…Hair follicle cannot be dissociated from sebaceous gland, because they display integrated working mechanism (Data ). In living mouse, a single placode gives rise to hair follicle and its associated sebaceous glands, and all mouse lines with sebaceous deficiency present progressive scarring alopecia (s39, s40) . This integrated development indicates an ancient association, but not a gland‐to‐hair evolution as previously postulated (s41).…”

Sebaceous lipids are essential for water repulsion, protection against UVB-induced apoptosis, and ocular integrity in mice

“…This is initially surprising, as previous mouse lines with SG deficiency, including the classic asebia mutant (Schneider, 2015) and numerous mouse lines with targeted mutations in genes such as Sox9 (Vidal et al, 2005), Dgat1 (Chen et al, 2002) or Scd1 (the asebia-associated gene; Miyazaki et al, 2001), commonly present with alopecia or at least severe pathological changes of the hair follicle. In fact, although SGs can form and function in the absence of a hair follicle, the latter might neither form nor function normally in the absence of an SG (Stenn et al, 2008).…”

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

“…The asebia mouse ( Scd1 ab ), which more correctly was the first hypoplastic sebaceous gland mouse model, provided the prototype pathogenesis for PCA . The first allele was discovered in 1965, and the mice have been used for over 50 years to study sebaceous gland function . Identification of the mutated gene, stearoyl‐Coenzyme A desaturase 1 ( Scd1 ), followed by detailed phenotyping suggested that secretions from the sebaceous gland did not degrade the hair follicle inner root sheath adequately and the growing hair follicle and shaft could not push the shaft out at a normal rate resulting in unusually long hair follicles.…”

“…[62] The first allele was discovered in 1965, [71] and the mice have been used for over 50 years to study sebaceous gland function. [72] Identification of the mutated gene, stearoyl-Coenzyme A desaturase 1 (Scd1), [73] followed by detailed phenotyping [62] suggested that secretions from the sebaceous gland did not degrade the hair follicle inner root sheath adequately and the growing hair follicle and shaft could not push the shaft out at a normal rate resulting in unusually long hair follicles. When the follicles entered catagen, they failed to contract normally such that telogen follicles were unusually long, often being misdiagnosed as prolonged anagen, sometimes rupturing at the bulb end.…”