The C3H/HeJ mouse and DEBR rat models for alopecia areata: review of preclinical drug screening approaches and results

Abstract

The C3H ⁄ HeJ inbred mouse strain and the Dundee Experimental Bald Rat (DEBR) strain spontaneously develop adult onset alopecia areata (AA), a cell-mediated disease directed against actively growing hair follicles. The low frequency of AA and the inability to predict the stage of AA as it evolves in the naturally occuring C3H ⁄ HeJ model of AA can be converted into a highly predictable system by grafting full thickness skin from AA-affected mice to normal haired mice of the same strain. The rat DEBR model develops spontaneous AA at a higher frequency than in the mouse model but they are more expensive to use in drug studies owing to their larger size. Regardless of the shortcomings of either model, these rodent models can be used succesfully to screen novel or approved drugs for efficacy to treat human AA. As the pathogenesis of AA follows the canonical lymphocytic co-stimulatory cascade in the mouse AA model, it can be used to screen compounds potentially useful to treat a variety of cellmediated diseases. Efficacy of various agents can easily be screened by simply observing the presence, rate, and cosmetic acceptability of hair regrowth. More sophisticated assays can refine how the drugs induce hair regrowth and evaluate the underlying pathogenesis of AA. Some drugs commonly used to treat human AA patients work equally as well in both rodent models validating their usefulness as models for drug efficacy and safety for humanAA.Key words: alopecia areata -animal modeldinitrochlorobenzene -diphenylcyclopropenone -reviewsquaric acid dibutyl esterase -treatment Please cite this paper as: The C3H ⁄ HeJ mouse and DEBR rat models for alopecia areata: review of preclinical drug screening approaches and results.

Presence of Alternaria in Scalp of Patients with Alopecia Areata: Triggering Factor or Coexistence?

“…This is in agreement with [11], who reported that Alternaria are keratinolytic, dematiaceous (melanin-producing) fungi that are only occasionally implicated in opportunistic human diseases, such as skin and nail infections [12]. This can be explained by the hypothesis that antigens associated with melanogenesis are suggested to be potential triggers of autoimmunity in AA [13]. Thus, melanin producing fungi including Alternaria species may have a potentiating role in autoimmune mechanism of AA [14].…”

Epidermal Cadm1 Expression Promotes Autoimmune Alopecia via Enhanced T Cell Adhesion and Cytotoxicity

“…Alopecic wild type mice exhibited lymphocyte accumulation at hair follicle bulbs and sebaceous glands (Fig. 7A, A9) (8). In contrast, lymphocytes were found in K14Cadm1 alopecic skin along the full length of the hair follicles, including the bulge and extending to the underlying muscle layer (Fig.…”

“…The C3H/HeJ inbred mouse strain is a widely accepted experimental model of autoimmune alopecia initiation and progression, as up to 20% of aged C3H/HeJ mice spontaneously develop the disease (7,8). Mice exhibit a characteristic nonscarring, inflammatory cell-dependent hair loss that closely resembles human autoimmune alopecia.…”

“…Mice exhibit a characteristic nonscarring, inflammatory cell-dependent hair loss that closely resembles human autoimmune alopecia. Mononuclear infiltrates occur within the hair follicles, which fail to enter anagen and subsequently degenerate (7,8). Alopecia can be induced in unaffected mice by full-thickness skin grafts or peripheral lymph node-derived cell transfer from affected individuals (9,10).…”

Comparative analysis of cutaneous drug reactions among different fluoroquinolones: an experimental study

“…7,8 Mouse is also used as models for alopecia areata for review of preclinical drug screening. 9 Taking all these into account we used Mice as the animal model for study of relative incidence of cutaneous drug reactions among different commonly used Fluoroquinolones. …”