also occurs in transgenic animals is not known. Activation effects are likely to reveal themselves as dominant mutations that can have a variety of phenotypic consequences, from derailing normal development to causing a high rate of cancer later in life.
Even if expressed as desired, the genetic engineering itself can often have unexpected effects on the physiology of the engineered organism. One example of such an unwanted effect relates to the xenotransplantation model described above. The galactosyl transferase deficiency in humans, which leads to hyperacute rejection of organ from pigs, also is thought to offer a level of protection against zoonotic infection by enveloped viruses (Weiss, 1998). This effect occurs because the surface proteins of viruses produced by nonhuman cells are also engineered with the same galactosyl-galactose structure found on host cell proteins, and are therefore subject to the same potent immune response. This response would lead to the rapid elimination of viruses transmitted from animals before infection could occur. Pigs that are engineered by knockout of this gene would, therefore, have the potential to transmit viruses, such as influenza, much more readily to human handlers. A related concern is that human cell-surface proteins introduced into animal species as transgenes could render those animals susceptible to human viruses, increasing their risk of disease and providing alternative hosts for the spread of human disease. For example, the human poliovirus receptor (CD155) renders mice susceptible to poliovirus infection when introduced as a transgene (Racaniello and Ren, 1994). Also, the human complement-response modifying proteins CD46 and CD55, which are being introduced into pigs to protect xenografts from rejection, also serve as receptors for human viruses—measles and Coxsackie, respectively (Weiss, 1998). Their presence in transgenic pigs not only could render these animals susceptible to infection by the human viruses, but also could provide a new evolutionary pathway for adaptation of pig viruses to human cells. Since the receptors for many other viruses have not yet been identified, the potential for this sort of surprise exists whenever a human cell-surface protein is introduced into another animal species.
Vector constructs used for creating transgenic organisms usually contain genes other than the desired transgene. These genes are typically drug-resistance markers obtained from bacteria, which also can confer resistance to the same or similar drugs on eukaryotic cells. The neo gene encoding