Target Discovery and Validation Reviews and Protocols

Louis-Marie Houdebine, Houdebine, Louis-Marie

Transgenic animals have become a key tool in functional genomics to generate models for human diseases and validate new drugs. Transgenesis includes the addition of foreign genetic information to animals and specific inhibition of endogenous gene expression. Recently, animal models provided novel insight and significantly improved our understanding of the initiation and perpetuation of human diseases. Moreover, they are an invaluable tool for target discovery, validation, and production of therapeutic proteins. However, despite the generation of several transgenic and knockout models, obtaining relevant models still faces several theoretical and technical challenges. Indeed, genes of interest are not always available and gene addition or inactivation sometimes does not allow clear conclusions because of the intrinsic complexity of living organisms or the redundancy of some metabolic pathways. In addition to homologous recombination, endogenous gene expression can be specifically inhibited using several mechanisms such as RNA interference. Here, some animal models are described to illustrate their importance in biomedical research. Moreover, guidelines for generation of these animals are presented.