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 two defects have the potential to make high dietary vitamin A levels toxic in some B6 substrains while not affecting most other commonly used inbred strains.

A Mouse Model of Clonal CD8+ T Lymphocyte-Mediated Alopecia Areata Progressing to Alopecia Universalis

“…Characteristics of cicatricial alopecia which can normally be found in B6 mice were also seen (29), though the microscopic lesions of AA predominated. Lymphocyte infiltrates were observed in and around anagen and late catagen stage hair follicles, extending from the bulge downward to just above the hair bulb (Fig.…”

Epidermal Fatty Acid Binding Protein Promotes Skin Inflammation Induced by High-Fat Diet

“…Although aged mice with C57BL/6 genetic background are known to be susceptible to inflammatory skin lesions, such as ulcerative dermatitis (Kastenmayer et al, 2006; Williams et al, 2012), a high incidence of skin lesions observed only in the obese mice in our experimental settings clearly suggests that, besides genetic factors, the HFD significantly contributes to skin inflammation. Given the unknown etiology of ulcerative dermatitis syndrome in mice (Duarte-Vogel and Lawson, 2011; Sundberg et al, 2011), and the poor understanding of obesity-associated inflammatory skin diseases in human (Yosipovitch et al, 2007; Shipman and Millington, 2011; Scheinfeld, 2004; Mathur and Goebel, 2011; Mirmirani and Carpenter, 2014), we set out to dissect the cellular and molecular mechanisms of how the HFD, as a major environmental factor, promotes inflammatory skin lesions. Here, we provide evidence to establish E-FABP as a new molecular sensor in triggering HFD-induced skin inflammation.…”

Crisp1 and alopecia areata in C3H/HeJ mice

“…CRISP1 was also undetectable in mutant mice in which the HSM did not form properly (mutations in the Foxq1 and Soat1 genes) and do not develop AA spontaneously (Wu et al, 2010; Wu et al, 2013). Targeted mutant mice, in which the Crisp1 gene had been inactivated, did not have any lesions affecting the hair follicles or hair shafts other than scattered follicular dystrophy, mild ulceration, or subepidermal fibrosis consistent with B6 alopecia and dermatitis, a common strain specific background disease in the C57BL/6 substrains (Sundberg et al, 2011). …”