Transgenic Animals Are Animals Carrying Foreign Genes

Experimental advances in gene transfer techniques have made it possible to introduce genes into animals by transfection. Transfection is defined as the uptake or injection of plasmid DNA into recipient cells. Animals that have acquired new genetic information as a consequence of the introduction of foreign genes are termed transgenic. Plasmids carrying the gene of interest are injected into the nucleus of an oocyte or fertilized egg, and the egg is then implanted into a receptive female. The technique has been perfected for mice (see figure). In a small number of cases—10% or so—the mice that develop from the injected eggs carry the transfected gene integrated into a single chromosomal site. The gene is subsequently inherited by the progeny of the transfected animal as if it were a normal gene. Expression of the donor gene in the transgenic animals is variable because the gene is randomly integrated into the host genome and gene expression is often influenced by chromosomal location. Nevertheless, transfection of animals has produced some startling results, as in the case of the transfection of mice with the gene encoding the rat growth hormone (rGH). The transgenic mice grew to nearly twice the normal size. Growth hormone levels in these animals were several hundred times greater than normal. Similar results were obtained in transgenic mice transfected with the human growth hormone (hGH) gene. The biotechnology of transfection has been extended to farm animals, and transgenic chickens, cows, pigs, rabbits, sheep, and even fish have been produced. The first animal cloned from an adult cell, a sheep named Dolly, represented a milestone in cloning technology. Subsequent accomplishments include incorporation of the human gene encoding blood coagulation factor IX into sheep. Fetal sheep fibroblast cells were transfected with the human factor IX gene, nuclei from the transfected cells were transferred into sheep oocytes lacking nuclei, and these transgenic oocytes were placed in the uterus of receptive female sheep, which subsequently gave birth to transgenic lambs. The introduced factor IX transgene was specifically designed so that factor IX protein, a medically useful product for the treatment of hemophiliacs, would be expressed in the milk of the transgenic sheep. Similar successes in cows, which produce much more milk, has brought the potential for commercial production of virtually any protein into the realm of reality. Transfection technology also holds promise as a mechanism for “gene therapy” by replacing defective genes in animals with functional genes. Problems concerning delivery, integration and regulation of the transfected gene, including its appropriate expression in the right cells at the proper time during development and growth of the organism, must be brought under control before gene therapy becomes commonplace in humans.