title: Two mouse mutations mapped to chromosome 11 with differing morphologies but similar progressive inflammatory alopecia.
abstract: Alopecia is a common dermatological condition in humans and other mammals. Here, we present two similar but histologically distinct mouse models of scarring alopecia. Both mutant lines were generated using random genome-wide N-ethyl-N-nitrosourea mutagenesis, and both harbor dominant mutations on chromosome 11. In both mutants, there is an early onset of alopecia that progresses to nearly complete pelage hair loss in both males and females by 20 weeks of age. Histologically, there is an increased dermal cellularity due to inflammatory cell infiltration at 7-10 days of age. By 3 weeks of age, the epidermis is acanthotic and the dermis is approximately twice as thick as in control mice due to a substantial, mostly mononuclear, inflammatory cell infiltrate. This infiltrate becomes more perifollicular by 4-5 weeks of age but is localized differently in the two mutants. In alopecia 1 (Alo-1), the perifollicular infiltrate is confined to the portion of the follicle within the dermis, whereas in Alo-2, the infiltrate extends the full length of the follicle. Expression of major histocompatibility complex (MHC) class I on the follicular epithelium in the two mutants is much greater than that in non-mutants. Furthermore, MHC class I expression is localized differently in the two mutant lines and mirrors the pattern of the inflammatory infiltrate. Despite these differences, the clinical progression of alopecia is identical in both mutants. The early onset of the disease, predictable progression, and differences in inflammatory cell localization between the two mutants make these mice particularly useful models for inflammatory hair loss and autoimmune diseases in general.
authors.affiliation: Centre for Modeling Human Disease, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada. geoffrey.wood@utoronto.ca
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Wood
authors.forename: Ann
authors.initials: A
authors.lastname: Flenniken
authors.forename: Lucy
authors.initials: L
authors.lastname: Osborne
authors.forename: Craig
authors.initials: C
authors.lastname: Fleming
authors.forename: Igor
authors.initials: I
authors.lastname: Vukobradovic
authors.forename: Lily
authors.initials: L
authors.lastname: Morikawa
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.forename: Rebecca
authors.initials: R
authors.lastname: Porter
authors.forename: S Lee
authors.initials: SL
authors.lastname: Adamson
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
authors.forename: Colin
authors.initials: C
authors.lastname: McKerlie
mesh_terms: D000505:Alopecia / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D003872:Dermatitis / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D018859:Hair Follicle / Q000276:immunology / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016296:Mutagenesis
chemical_list: D015395:Histocompatibility Antigens Class I; D018799:Intercellular Adhesion Molecule-1