Functional analysis of the non-HLA genes within major histocompatibility complex (MHC) region with the use of gene-targeted mice

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Since the discovery of the relationship between the geno-types of major histocompatibility complex (MHC) and susceptibility to many diseases, including autoimmune diseases, functional analysis of the genes within MHC region has been considered to be one of the most important issues for the better understanding of the processes involved in the development of many diseases. In order to reveal the mechanisms underlying the relationship between major histocompatibility complex (MHC)-type and disease susceptibility, we have been working on the generation of mice in which immune-related genes within the MHC region are deleted (knockout mice) with the use of gene-targeting technology. In this study, we have especially focused on the analysis of two genes near the TNF/lymphotoxin locus, because this locus contains many genes relevant to the development of inflammation. For one gene, chimeric mice have been generated, and the targeting vector has been constructed for the other gene, We are now in the process of generation of knockout mice for these two genes, We believe that analysis of the phenotype of these mice will also lead to a clear understanding of the function of the genes relevant to the host defence mechanism.