Introduction of Human γ1 Immunoglobulin Genes into Fertilized Mouse Eggs1

A rearranged human γ 1 immunoglobulin gene was introduced into fertilized mouse eggs. The phage Ch4A-VCE-γ 1 was constructed by ligating an Eco RI and Bgl II fragment of pBR322-CESSV(CE-l) containing the VDJ region with an EcoRI and BamHI fragment of Ch4A-HJgγ 1 -10 containing the y constant region. About 200 copies of Ch4A-VCE-γ 1 genes were introduced into fertilized mouse eggs. Of 489 eggs injected with these genes, 319 survived and were transferred to oviducts of foster mothers. Thirtyeight mice were born and were screened for the presence of human γ 1 immunoglobulin genes by Southern blot hybridization. Five of these 38 mice had integrated human y immunoglobulin genes. None of the humanγ 1 copies in each mouse had undergone deletions or rearrangements as judged by the Southern blotting patterns for several restriction enzymes. Human γ 1 gene was present in several different tissues. All the mice tested so far transmit the human γ 1 gene to a fraction of their offspring in an autosomal dominant manner. Spleen cells from transgenic mice were analyzed for immunoglobulin production by reverse plaque assay or immunofluorescence staining of cytoplasmic immunoglobulin, but synthesis and secretion of human γ 1 chains could not be detected. No human γ 1 immunoglobulin mRNA was detected in the liver and spleen of a transgenic mouse. The presence of the human γ 1 inimunoglobulin gene appeared to have no effect on the expression of endogenous mouse immunoglobulin genes.