title: Primary follicular dystrophy with scarring dermatitis in C57BL/6 mouse substrains resembles central centrifugal cicatricial alopecia in humans.
abstract: A number of C57BL/6 (B6) substrains are commonly used by scientists for basic biomedical research. One of several B6 strain-specific background diseases is focal alopecia that may resolve or progress to severe, ulcerative dermatitis. Clinical and progressive histologic changes of skin disease commonly observed in C57BL/6J and preliminary studies in other closely related substrains are presented. Lesions develop due to a primary follicular dystrophy with rupture of severely affected follicles leading to formation of secondary foreign body granulomas (trichogranulomas) in affected B6 substrains of mice. Histologically, these changes resemble the human disease called central centrifugal cicatrical alopecia (CCCA). Four B6 substrains tested have a polymorphism in alcohol dehydrogenase 4 (Adh4) that reduces its activity and potentially affects removal of excess retinol. Using immunohistochemistry, differential expression of epithelial retinol dehydrogenase (DHRS9) was detected, which may partially explain anecdotal reports of frequency differences between B6 substrains. The combination of these 2 defects has the potential to make high dietary vitamin A levels toxic in some B6 substrains while not affecting most other commonly used inbred strains.
authors.affiliation: DVM, PhD, The Jackson Laboratory, Bar Harbor, ME 04609-1500, USA. john.sundberg@jax.org
authors.forename: J P
authors.initials: JP
authors.lastname: Sundberg
authors.forename: D
authors.initials: D
authors.lastname: Taylor
authors.forename: G
authors.initials: G
authors.lastname: Lorch
authors.forename: J
authors.initials: J
authors.lastname: Miller
authors.forename: K A
authors.initials: KA
authors.lastname: Silva
authors.forename: B A
authors.initials: BA
authors.lastname: Sundberg
authors.forename: D
authors.initials: D
authors.lastname: Roopenian
authors.forename: L
authors.initials: L
authors.lastname: Sperling
authors.forename: D
authors.initials: D
authors.lastname: Ong
authors.forename: L E
authors.initials: LE
authors.lastname: King
authors.forename: H
authors.initials: H
authors.lastname: Everts
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000505:Alopecia / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D000818:Animals; D006099:Granuloma / Q000473:pathology; D018859:Hair Follicle / Q000473:pathology*; D007150:Immunohistochemistry / Q000662:veterinary; D051379:Mice; D008810:Mice, Inbred C57BL; D012376:Rodent Diseases / Q000235:genetics / Q000473:pathology*; D013045:Species Specificity; D014801:Vitamin A / Q000378:metabolism
chemical_list: D014801:Vitamin A; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; C105552:alcohol dehydrogenase IV; C022520:retinol dehydrogenase