Utilization of genetically altered animals in the pharmaceutical industry

The study of transgenic and gene-deleted (knockout) mice provides important insights into the in vivo function and interaction of specific gene produc ts. Within the pharmaceutical industry, genetically altered mice are used p redominantly in discovery research to characterize the diverse functions of one or multiple gene products or to establish animal models of human disea se for proof-of-concept studies. We recently used genetically altered anima ls in drug discovery to examine the NF-kappa B family of transcriptional re gulatory genes and to elucidate their essential role in the early onset of immune and inflammatory responses. Transgenic and knockout mice are also us eful in drug development, because questions regarding risk assessment and c arcinogenesis, xenobiotic metabolism, receptor- and ligand-mediated toxicit y, and immunotoxicity can be evaluated using these genetically altered mice . For example, the p53 knockout mouse is one of several genetically altered mice whose use may increase the sensitivity and decrease the time and cost of rodent carcinogenicity bioassays. As with any experimental model system , data obtained from genetically altered mice must be interpreted carefully . The complete inactivation of a gene may result in altered expression of r elated genes or physiologic compensation for the loss of the gene product. Consideration must also be given to the genetic background of the mouse str ain and the impact of strain variability on disease or toxicity models. Des pite these potential limitations, knockout mice provide a powerful tool for the advancement of drugs in the pharmaceutical industry.