Kayako Hira

NC/Nga Mice: A Mouse Model for Atopic Dermatitis

Atopic dermatitis (AD) is a common pruritic disease that occurs primarily in infancy and childhood. AD is characterized by itching and the patient having an individual or family history of atopic diseases. Although AD is also frequently associated with elevated serum IgE levels and with common environmental factors contributing to its pathogenesis, the etiology of AD is still unknown. We examined NC/Nga mice (NC mice) that showed AD-like skin lesions with aging as a possible mouse model for AD. NC mice were maintained under conventional (Conv) or specific pathogen-free (SPF) conditions. Clinical symptoms, serum IgE levels and histopathology of the skin were compared between these 2 groups, and we explored their application as a model of human AD. It was found that the skin lesions of inbred NC mice were clinically and histologically very similar to human AD when the mice were raised under Conv conditions, but not under SPF conditions, and we assumed that some kinds of environmental factors might trigger AD-like signs and symptoms in NC mice. To further investigate the pathophysiology and treatment of AD, a suitable animal model is absolutely required, and NC mice are very useful for this purpose.

Expression of DNMT-1 in patients with atopic dermatitis.

DNA methylation is known to play an important role in gene transcription and alterations of methylation that contribute to the development of certain disorders such as cancer, immunodeficiency, and autoimmune diseases. We investigated the DNA methylation profiles in patients with atopic dermatitis (AD). Messenger RNA (mRNA) levels for DNA methyltransferase-1 (DNMT-1) in peripheral blood mononuclear cells (PBMC) were examined using a real-time quantitative polymerase chain reaction method. The levels of DNMT-1 mRNA were significantly lower in PBMC from the AD patients who had higher serum IgE levels compared with normal controls. Our observations suggest that suppression of DNMT-1 might be related to the pathogenesis of AD, especially in whom serum IgE level is high. This is the first report of DNMT-1 expression in AD patients.

Establishment and characterization of a murine mast cell line derived from NC/Nga mice.

A cell line, termed NCJ, was established from the bone marrow-derived mast cells (BMMCs) of NC/Nga mice that are mouse models for atopic dermatitis. NCJ cells expressed FcΕRI and c-kit and showed a metachromasia of the granules with a toluidine blue-positive and safranin-negative staining pattern that is characteristic for immature-type mast cells. Interestingly, NCJ cells showed proliferation independent of IL-3, which was associated with constitutive phosphorylation of Raf-1 and Erk kinases. Although NCJ cells had several characteristics of mast cells, we failed to detect FcΕRI-mediated β-hexosaminidase release and its histamine content. These findings indicated that NCJ cells represented a mast cell line with an immature phenotype and the ability to proliferate in the absence of mast cell growth factors. NCJ cells might thus be useful to study the molecular basis of mast cell proliferation.