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...

Inbred mice provide a unique tool to study aging populations because of the genetic homogeneity within an inbred strain, their short life span, and the tools for analysis which are available. A large-scale longitudinal and cross-sectional aging study was conducted on 30 inbred strains to determine, using histopathology, the type and diversity of diseases mice develop as they age. These data provide tools that when linked with modern in silico genetic mapping tools, can begin to unravel the complex genetics of many of the common chronic diseases associated with aging in humans and other mammals. In addition, novel disease models were discovered in some strains, such as rhabdomyosarcoma in old A/J mice, to diseases affecting many but not all strains including pseudoxanthoma elasticum, pulmonary adenoma, alopecia areata, and many others. This extensive data set is now available online and provides a useful tool to help better understand strain-specific background diseases that can complicate interpretation of genetically engineered mice and other manipulatable mouse studies that utilize these strains.

Angora is an autosomal recessive mouse mutation caused by a deletion of approximately 2 kilobases in the fibroblast growth factor 5 (Fgf5) gene. Phenotypically, homozygous angora (Fgf5go/Fgf5go) mice have excessively long truncal hair and can be differentiated from heterozygous (+/Fgf5go) and wild-type (+/+) littermates by 21 days of age. Abnormal hair length is due to a prolongation of the anagen phase of the hair cycle of approximately 3 days. In addition, widely scattered hair follicles produce structurally defective hair shafts that twist within the follicle, presumably causing secondary hyperplasia of the outer root sheath and epidermis adjacent to the follicle. These follicular abnormalities were accentuated by immunohistochemical detection of mouse specific keratin 6, a nonspecific marker of epidermal hyperplasia. These abnormalities could be identified from birth throughout life in angora mice genotyped by polymerase chain reaction techniques. Moreover, the long truncal hair phenotype was maintained in skin grafted onto C.B-17/Sz-scid/scid mice that had normal pelage hairs and hair cycles, suggesting that circulating or diffusible humoral factors regulating the mouse hair cycle are not involved in this mutation. The angora mutation provides another useful mouse model for studying the hair cycle and its modulation.

The Mouse Disease Information System (MoDIS) is a data capture system for pathology data from laboratory mice designed to support phenotyping studies. The system integrates the mouse anatomy (MA) and mouse pathology (MPATH) ontologies into a Microsoft Access database facilitating the coding of organ, tissue, and disease process to recognized semantic standards. Grading of disease severity provides scores for all lesions that can then be used for quantitative trait locus (QTL) analyses and haplotype association gene mapping. Direct linkage to the Pathbase on line database provides reference definitions for disease terms and access to photomicrographic images of similar diagnoses in other mutant mice. MoDIS is an open source and freely available program (The Jackson Laboratory, Bar Harbor, ME; http://research.jax.org/faculty/sundberg/index.html). This provides a valuable tool for setting up a mouse pathology phenotyping program.

Chronic proliferative dermatitis (cpdm) is a spontaneous mutation that results in eosinophilic inflammation in multiple tissues, including the skin. To determine the mechanisms underlying the eosinophilic inflammation, the expression of cytokines in the skin was determined. There was increased expression of IL‐4, IL‐5, IL‐13, and granulocyte‐macrophage colony‐stimulating factor in the skin of cpdm/cpdm mice, and no change in IL‐10 and TNF expression. Supernatants of cultured spleen cells of cpdm/cpdm mice contained an increased amount of IL‐5 and IL‐13, and a decreased amount of IFN‐γ. The ability of the cpdm/cpdm mice to mount a delayed‐type hypersensitivity response was greatly reduced. These data are consistent with impaired type 1 and excessive type 2 cytokine production in cpdm/cpdm mice. The significance of this imbalanced cytokine production was evident in the efficacy of systemic treatment of cpdm/cpdm mice with IL‐12. Mutant mice treated for 3 weeks with IL‐12 had minimal changes in the skin as opposed to the severe dermatitis in mice treated with the vehicle. Treatment with IL‐11, which opposes the effect of IL‐12, had no effect.