Asebia-2J (Scd1ab2J): A New Allele and a Model for Scarring Alopecia

Abstract

A spontaneous, autosomal, recessive mouse mutation exhibiting mild scaly skin, progressive scarring alopecia, slightly runted growth, and photophobia arose at The Jackson Laboratory in 1993 in the inbred mouse strain DBA/1LacJ. Because this mutant mouse showed genetic, anatomical, and laboratory similarities to the asebia mutation, crosses were done between the new mutant and mice carrying the asebia-J allele. Because the F1 offspring were affected, indicating the two mutants were allelic, the new mutation was named asebia-2J. Careful histological analysis of skin development of mice homozygous and heterozygous for either asebia-J or asebia-2J revealed that both types of mutant mice are very similar regardless of their background. Notable histopathological features of mice homozygous for either allele included extreme sebaceous gland hypoplasia, abnormally long anagen follicles, retained inner root sheath, hair fiber perforation of the anagen follicle base, and progressive follicular replacement by scarring. In this article we present a new pathogenetic hypothesis based on the importance of the sebaceous gland in hair fiber sheath dissociation: in the absence of a functional sebaceous gland the hair follicle is destroyed. The cutaneous pathology of this mutant mouse underscores the importance of the sebaceous gland to follicular biology and presents an animal model for studying the human scarring alopecias, which characteristically begin with sebaceous gland ablation. The original asebia mouse mutation, an autosomal recessive trait characterized by hypoplastic sebaceous glands, arose spontaneously more than 30 years ago in a colony of BALB/cCrglGa mice.1 Although in the original study it was thought that these mice lacked sebaceous glands, hence the name asebia (gene symbol ab), later studies showed that sebaceous glands and modified sebaceous glands (meibomian, preputial, clitoral, and ceruminous glands) are present but hypoplastic.2-4 In 1968, a similar mutation arose spontaneously in the BALB/cJ inbred strain at The Jackson Laboratory; this mutant was found to be allelic to ab (Dr. S. J. Mann) and was named asebia-J (ab J ). Mice carrying the ab J mutation were out-crossed to C3H/Di and back-crossed to F8 5 from which time the mutant was maintained by brothersister matings (P. Lane, personal communication) on the inbred strain ABJ/Le. 6 The ab J remutation was mapped to mouse chromosome 19. 5Compared to heterozygous or normal littermates, ab J mutants are small and have a hunched back. Adult homozygous asebia mice develop generalized alopecia and scaly skin. Although the hair shafts form normally, 3,7 they are sparse and short.8 Histological studies have shown that the epidermis is thickened from birth with enlarged intercellular spaces. Hair follicles are excessively long extending at a sharp angle into the deep subcutis. All growth phases of the cycle, anagen, catagen, and telogen, last longer than those of the controls. 2,8 Abnormalities in the inner root sheath (IRS) include the absence of typical transve...

Normal Fur Development and Sebum Production Depends on Fatty Acid 2-Hydroxylase Expression in Sebaceous Glands

“…This conclusion is mainly based on the analysis of the asebia mouse (36,37), which has a deficiency in the Scd1 gene (encoding the desaturase responsible for C18:1-CoA synthesis), causing a degeneration of SG (8,36,37). This is accompanied by prolonged hair cycle phases, including the prolonged growing phase of hair follicles and alopecia (38,39). It has been proposed that many (scarring) alopecias of unknown origin might be caused by primary defects in the SG (10).…”

“…Delayed Hair Fiber Exit Because of Impaired SG Function-FA2H-deficient mice show some similarities to the asebia mouse mutant, which exhibits delayed hair fiber exit from follicles, caused by cornified cell plugs in the follicula ostia (38), possibly because of impaired sebum production. A similar, 2-day-delayed hair fiber exit was observed in mice deficient in Fig.…”

Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism

“…In adult mice, Scd1 is found in presebocytes and Scd3 in mature sebocytes [6]. Mice with a targeted deletion of Scd1 or naturally occurring asebia mutation have hypoplasia of the sebaceous and meibomian glands resulting in alopecia and closed eye fissure [2,41,68]. The hypoplasia of sebaceous glands in adult scd1-deficient mice results in loss of Scd3 expression in the skin [6].…”

“…Scd2 was found to be the predominant hepatic SCD isoform in neonates, but hepatic Scd1 expression progressively increases in the 21 days postbirth to become the major hepatic SCD isoform [12]. [68,70], have a dysfunctional epidermal lipid barrier resulting in increased transepidermal water loss. Interestingly, topical application of an artificial lipid barrier partially rescued the abnormal metabolic rate, water loss and heat loss observed in Scd1-deficient mice [69 • ].…”

Alopecias cicatriciais primárias: revisão de achados histopatológicos de 37 pacientes do Departamento de Dermatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo no período de 2000 a 2005

“…A interpretação do tempo de curso dos estudos sugere que a mudança na composição do sebo resultaria em uma falha anormal da descamação da bainha radicular interna, evitando o egresso do cabelo durante a fase catágena, desta forma o bulbo capilar seria perfurado pelo eixo do cabelo e o processo inflamatório seria induzido (Sundberg, 2000).…”