Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice

Abstract

Atopic dermatitis (AD) usually develops in patients with an individual or family history of allergic diseases, and is characterized by chronic relapsing inflammation seen especially in childhood, association with IgE hyperproduction and precipitation by environmental factors. However, the exact etiology of AD has been unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is required. We found that skin lesions, which were clinically and histologically very similar to human AD, spontaneously appeared on the face, neck, ears and dorsal skin of inbred NC/Nga mice when they were raised in non-sterile (conventional) circumstances, but not under specific pathogen-free conditions. Plasma levels of total IgE in conventional NC/Nga mice were markedly elevated from 8 weeks of age, correlating with clinical skin severity of dermatitis. Immunohistochemical examination of the skin lesion showed increased numbers of mast cells and CD4+ T cells containing IL-4 necessary for IgE synthesis. Thus, NC/Nga mice suffered from dermatitis very similar to human AD with IgE hyperproduction, which may be triggered by some environmental factor(s).

Prevention and regression of atopic dermatitis by ointment containing NF-kB decoy oligodeoxynucleotides in NC/Nga atopic mouse model

“…In addition, the control mice exhibited marked spongiosis and infiltration of cells. Moreover, as previously reported, 16,17 immunohistochemical examination of the skin lesions showed an increase in the number of mast cells containing IL-4 which are necessary for IgE synthesis. Interestingly, the number of infiltrated mast cells was significantly decreased in the dermis of mice transfected with NF-kB decoy ODN as compared with mice transfected with scrambled decoy ODN in toluidine blue (TB)-stained sections ( Figure 5, scrambled decoy ODN: 16.0 ± 2.3 cells/field, NFkB decoy ODN: 1.8 ± 0.7 cells/field, P Ͻ 0.01).…”

“…[16][17][18] The skin lesions of inbred NC mice are clinically and histologically very similar to those of human atopic dermatitis when the mice are raised under conventional conditions, but not under SPF conditions. Skin lesions spontaneously appear on the face, neck, ears and dorsal skin of inbred NC/Nga mice in non-sterile (conventional) conditions.…”

Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice

“…Cytokine and IgE levels in the skin lesion of NC/Nga mice NC/Nga mice have been reported to develop eczematous skin lesions when kept in conventional surroundings [14][15][16] but cytokine levels in the lesions of NC/Nga mice are not reported. IL-10, IL-4, and IgE levels in the lesions were determined in mice kept under conventional and SPF conditions for different feeding periods.…”

“…Matsuda et al 14 proposed that the NC/Nga mouse would make an excellent animal model for human AD. When kept in specific pathogen-free (SPF) conditions, [14][15][16] the mice remain healthy. But when kept under conventional conditions, they started to scratch themselves at about 8 weeks, at which time their skin became dry and scaly.…”

“…In addition, the level of IgE in the blood gradually increases to high levels. 2 Although these immunological, histological, and biochemical changes of NC/Nga mice kept in conventional conditions resemble human AD, 14 the mechanisms are not fully clear yet.…”