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Introduction of a Cloned Gene into Fertilized Mouse Eggs and its Expression *

Abstract In order to analyze the role of enhancer sequence for the tissue‐specific and stage specific expression of immunoglobulin gene in normal diploid cells we have introduced cloned human y1 immunoglobulin genes into fertilized mouse eggs. Human y1 genes lacking enhancer sequence were not expressed in any tissues of transgenic mice. On the other hand human y1 genes containing enhancer sequence were expressed only in B lymphocytes. Levels of HIGI mRNA and percentage of human y chain producing cells in spleen cells were increased up to 50 times after treatment with lipopolysaccharide but not with Concanavalin A, suggesting B cell specific and regulated expression of HIGI gene. Human y chain producing cells were only found in the periphery of germinal center of the white pulp in histological section of the spleen suggesting stage‐specific expression. Human y chains appeared to be coupled with mouse light chains to form a complete IgG molecule and are secreted into cell supernatant. The production and secretion of endogenous immunoglobulin heavy and light chains in transgenic mice appeared to be the same as in normal mice. About one‐seventh of spleen cells that are producing endogenous mouse heavy chain produced human y1 chain at the same time. But no cell which produce only human y chain was observed. These results suggest that human γ chain expression had no effect on mouse immunoglobulin expression.