Identification of cells or cell lineage responsible for atopic dermatitis-like skin lesions in model mice for human diseases by means of TRECK method

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Atopic dermatitis (eczema : AD) is pruritic, chronic and relapsing inflammatory skin disease with predominantly childhood onset, but the symptoms can persist or begin in adulthood. It is also the most common cause of occupational skin disease in adults. Atopic dermatitis is associated with various immunological abnormalities and multiple environmental factors. Animal models are powerful tools to understand the bases and therapy of complex diseases. The NC/Nga inbred strain (NC), established from Japanese fancy mice in 1957, exhibits spontaneous severe dermatitis. The phenotypes of skin lesions in NC mice match the symptoms of the human atopic dermatitis, such as itching, erythema and hemorrhage with high titers of immunogloblin E (IgE) for various allergens. A similar skin inflammation has been observed in Stat6 deficient NC congenic mice with practically no IgE production. Genetic approaches indicate that numerous inherited factors can be responsible for the induction of skin inflammation. Genetically, the NC strain belongs to the Mus musculus domesticus group, which includes widely used laboratory strains, such as C57BL/6J.Many attempts has been made to identify genes responsible for the AD-like skin lesions shown by NC mice, and only one major QTL locus named derm1 has been identified (Kohara et al. Immunogenetics, 1991). The locus identification is not so easy because any allergens for the spontaneous skin lesions of NC mice have not been identified so far and other QTLs than the major one showed little genetic effects for the disease. We tried to do an alternative method for identification of cellular and genetic bases of the diseases : the method is called TRECK (Toxin-Receptor Mediated Cell Knockout) method. The TRECK method has been developed by Kohno and his collaborators (Saito et al. Nature Biotech, 2001). We applied this method to deplete cells possibly responsible for the skin lesions of NC mice. The research is now still in progress.