Chimeric chickens can be produced by injecting embryonic stem (ES) cells into recipient embryos in newly laid, unincubated eggs. The embryonic stem cells contribute to all somatic tissues and sporadically to the germline. The ratio of embryonic stem cell-derived and recipient-derived contributions to the germline can be manipulated by increasing the population of ES cell-derived germ cells. Conversely, the ratio of ES cell derived and recipient derived germ cells can be altered by removing and/or deleting contributions to the germline from the recipient. This application describes technologies to enhance the contribution of ES cell derived germ cells and reduce the contribution of the recipient embryo to the germline. It is anticipated that this shift in the ratio of ES cell-derived to recipient-derived germ cells will produce chimeras that have a larger number of gametes from the embryonic stem cell lineage. If the embryonic cells are carrying transgenes encoding the production of foreign proteins, this technology should provide a robust system for the establishment of founder transgenic chickens that deposit novel proteins in their eggs. The egg is an ideal repository for pharmaceutically important proteins because the egg is a sterile package, each hen lays approximately 300 eggs per year, technology for housing a few or many hens under specific pathogen free conditions is well known, fractionation of proteins in eggs is well understood, and the glycosylation pattern of chickens is similar to that of humans. These attributes make chickens an attractive option for the large-scale production of therapeutic proteins such as monoclonal antibodies.
Thesaurus Terms: busulfan, drug resistance, embryonic stem cell, gene expression, genetically modified animal, glutathione transferase, protein engineering actin, chicken, chimeric protein, expression cloning, genetic enhancer element, genetic promoter element, germ cell animal tissue, biotechnology, human genetic material tag, human tissue, transfection
