Melanocyte and gonad activity as potential severity modifying factors in C3H/HeJ mouse alopecia areata

Abstract

Circumstantial evidence has previously suggested gonad derived steroid hormones and melanogenesis related antigens may modify human alopecia areata (AA). AA-like hair loss can be induced in C3H/HeJ mice after skin allografts from spontaneous AA-affected mice. This inducible model was used to evaluate hormones and hair follicle melanocyte presence as disease-severity modifiers. Ten females and 9 males were gonadectomized and received AA-affected allografts. All gonadectomized mice had 2-4 weeks delay in AA onset relative to non-gonadectomized controls. Two females and 4 males failed to develop any AA by 25 weeks after grafting. The experiment was repeated with gonadectomized female and male mice plus non-gonadectomized mice subcutaneously implanted with silastic capsules containing 80 microg 17beta estradiol or 10 mg 5alpha dihydrotestosterone, respectively. Five of 11 ovariectomized and 9 of 11 non-ovariectomized, estradiol supplemented females developed AA with extremely rapid progression. Three of 8 castrated, but none of 11 non-castrated, dihydrotestosterone-supplemented males expressed AA. In a separate study, 14 mice were freeze-branded, producing white hair on the dorsal lumbar region, and later received full-thickness allografts. Thirteen mice developed patchy pigmented and non-pigmented hair loss. One mouse developed diffuse, pigmented hair loss, but with white hair survival persisting 25 weeks after grafting. The results suggest that gonadal steroid hormones can modulate C3H/HeJ mouse AA where estradiol promoted rapid progression of AA while dihydrotestosterone increased resistance to AA onset. In general, both pigmented and non-pigmented C3H/HeJ mouse hair is susceptible to AA. Murine AA susceptibility and severity clearly involves an interplay between genetic and epigenetic factors.

Heat treatment increases the incidence of alopecia areata in the C3H/HeJ mouse model

“…Such grafting-induced onset of AA provides investigators with the ability to control onset of the disease in a large number of animals. It has facilitated investigations into the role of non-genetic factors that may affect AA susceptibility, such as gonadal steroid hormones and diet (McElwee et al 2001;McElwee et al 2003). In the current study, we applied heat treatment to C3H/HeJ mice to analyze how stress plays a role on the development of AA.…”

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

“…Control of certain melanocytic peptides is linked to immune response MHC loci, providing another possible point of control of AA by the MHC (109). However, since AA can develop in other substrains of mice with no obvious melanization of hair (white hair) (2), and in regions of white hair induced by dry ice branding in the AA graft model (89), it is unclear if targeting melanin related antigens is critical to the pathogenesis of all types of AA.…”

Alopecia areata

“…Sparing of white hair is a relative phenomenon; white hairs, although less susceptible to the disease, are not immune to it. In a mouse model where pigment loss was created in a focal manner using freeze branding, white hairs were not preferentially spared 122 . However, in humans, white hair sparing might reflect effects of the autoimmune attack on the bulb region during the period when pigment is produced 68 .…”