Atopic Dermatitis-Like Skin Lesions Induced by Topical Application of Mite Antigens in NC/Nga Mice

Abstract

Background: Atopic dermatitis (AD) is a chronic relapsing inflammation usually observed in patients with an individual or a familial history of atopic diseases, precipitated by environmental factors including mite antigens (Ag). However, the exact etiology of AD is unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is necessary. In this study, we developed a new animal model of AD induced by mite Ag in NC/Nga mice. Methods: We injected the extracts of mite Ag intradermally at the ventral side of the ear of SPF NC/Nga mice on days 0, 2, 4, 7, 9, 11, 14 and 16, and measured the clinical symptoms and the ear thickness. On day 18, we collected blood and submandibular lymph nodes (LN) of the immunized ear to perform a histochemical analysis, and to measure the plasma immunoglobulins and cytokines. Results: The NC/Nga mice immunized with mite Ag suffered from AD-like skin lesions including erythema followed by edema, excoriation and scaling. The histological and immunohistochemical examinations of the affected skin showed epidermal hyperplasia with hyperkeratosis, severe infiltration of CD4+ T lymphocytes, eosinophils and macrophages, and degranulation of mast cells. The total plasma IgE level was markedly elevated in mite Ag-treated mice. LN cells of mice immunized with mite Ag synthesized IgE in an Ag-dependent manner and secreted interleukin-4 (IL-4) and IL-5 but not interferon-γ. Conclusions: NC/Nga mice treated with mite Ag manifest clinical and immunological aspects similar to patients with AD, suggesting that this model is suitable for exploring the pathogenesis of human AD.

Tetragenococcus halophilus MN45 Ameliorates Development of Atopic Dermatitis in Atopic Dermatitis Model NC/Nga Mice

“…It has been reported that one strain of probiotics suppresses IL-17 production and may be useful in the treatment of Th17-mediated disease . NC/Nga mice, an inbred strain established from Japanese fancy mice, develop AD-like skin lesions under conventional care or upon repeated challenge with 2,4,6-trinitrochlorobenzene (picryl chloride, PiCl; Tokyo Kasei Kogyo, Tokyo, Japan) under specific pathogen free (SPF) conditions (Kato et al, 2005;Matsuda et al, 1997;Sasakawa et al, 2001;Segawa et al, 2008c). Induced dermatitis is accompanied by elevated serum IgE levels, increased expression of Th2-type cytokines, eosinophil accumulation in the lesions and frequent scratching behavior, which are characteristic features of human AD (Segawa et al, 2008b;Segawa et al, 2008c).…”

Mouse Models for Atopic Dermatitis Developed in Japan

“…Although hypersensitivity to some environmental factors is suggested to cause dermatitis, the precise factor remains unclear. The breakthrough identification of conditions to induce AD in NC mice was made by Morita and colleagues, who discovered that fur mites induced dermatitis associated with IgE hyperproduction in a substrain of mice, NC/Kuj (Morita et al, 1999), and the mite antigen-induced dermatitis was subsequently confirmed (Sasakawa et al, 2001). These lines of evidence suggested a new model system for antigen-induced dermatitis.…”

Therapeutic Effects of Gyokuheifusan on NC/Nga Mouse Model of Allergic Dermatitis

“…9,10) Under SPF conditions, ADlike skin lesions can be also caused by continuous administration of hapten. NC/Nga mice are used in several AD models, including spontaneous AD model, mite antigen-induced AD model [11][12][13] and picryl chloride (PiCl)-induced AD model. [14][15][16] We previously examined the immunomodulatory effects of GHS in a mouse model of ovalbumin (OVA)-induced asthma, a major Th2-dominantdisease.…”