The study of the pathogenesis of autoimmune disease, in which specific antibodies may be either the cause for or the consequence of disease, can be greatly improved by reducing the diversity of antibodies under investigation. This can be achieved very effectively in a transgenic mouse model. I addition, for a model of human disease, it is desirable to have a mouse with inducible heavy x light (HxL) chain genes chosen with specificity for a self antigen, e.g. to DNA, which allows for the analysis of various antibody characteristics (e.g, concentration, charge, affinity, class) at different stages of development. To create such a mouse for this specific purpose, we will generate a mouse transgenic for a transactivator and for immunoglobulin transgenes under a mouse transgenic for a transactivator and for immunoglobulin transgenes under a tetracycline-responsive promoter. In the presence of tetracycline in the drinking water (in concentrations much less than that present in the serum of mice and drink such water), the mice will not express any transgenic antibodies. However, after withdrawal from tetracycline, expression of transgenic antibodies will be induced. In this system, induction can be controlled over a range of five orders of magnitude. Our studies will focus on the development of the inducible monoclonal mouse model for use in lupus research; but this model also should be a useful example for the development of mice harboring any chosen specificity as models for other autoimmune diseases where a specific antibody response is suspected to be a cause.
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