Four diploid human cell types (lymphocytes, fibroblasts, amniotic fluid cells, and hepatocytes) were fused to mouse hepatoma cells, HH. HH synthesized and secreted several liver-specific gene products including albumin, transferrin, and alpha-fetoprotein. The resulting interspecific hybrids were compared to determine whether or not the pattern of human hepatic gene expression was similar when these various cells were fused with the mouse hepatoma line. The expression of six human hepatic genes was examined, including albumin, alpha-fetoprotein, ceruloplasmin, transferrin, alpha-1-antitrypsin, and haptoglobin. Albumin was most frequently expressed while alpha-fetoprotein was not detected in any of the hybrids studied. The patterns of expression of human serum proteins differed between the hybrid series. Hybrids derived from human fibroblasts produced primarily albumin, while those derived from lymphoblastoid cells and amniocytes had a higher frequency of clones secreting alpha-1-antitrypsin. The findings reported here suggest that the frequency of hybrid clones expressing human hepatic gene products and the array of proteins produced are influenced by the histogenetic state of the human parental cell type.
Human liver-specific gene products are expressed by hybrid cells resulting from the fusion of human amniocytes with mouse hepatoma cells. Amniocytes grown from human amniotic fluid have no detectable levels of secreted human albumin, transferrin, alpha-1 antitrypsin, or ceruloplasmin, while the mouse hepatoma line, HH--, secretes several mouse liver-specific gene products including transferrin and albumin. Fifty-five hybrids were isolated and analyzed for the expression of serum proteins by Ouchterlony double diffusion and Laurell immunoelectrophoresis. All hybrids continued to express mouse albumin and transferrin, and 29 hybrids from this series were found to express one or more human serum proteins. Activation of the human amniocyte genome provides a model for prenatal diagnosis of serum protein abnormalities.
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