Small Animal Test Systems for Screening

Abstract

Modern biology is founded on the observations and the analyses of simple and genetically tractable small animals. The nematode (Caenorhabditis elegans), the fruit fly (Drosophila melanogaster), the frog (Xenopus laevis) the fish (Danio rerio) and the mouse (Mus musculus) have been studied for decades by basic scientists to understand eukaryotes’ fundamental biological mechanisms. The ability to use these small animal models to study human disease is predicated on the molecular conservation during evolution and validated by the sequencing of the entire genomes of several animals, including human. Indeed, many cellular biochemical pathways regulating metabolism, proliferation, cell death, and cell survival are highly conserved among eukaryotic organisms. The use of tractable animal models provides the opportunity of complementing genetic sequencing with powerful tools for genetic manipulation. This integrated approach results in an unprecedented, refined and comprehensive molecular understanding of complex cellular networks. The genetic analysis of signaling pathways regulating cellular responses in small animals has unveiled key molecular mechanisms that are altered in human pathologies such as cancer and diabetes. Today, these same animal models are cornerstones of modern drug discovery programs and are used to discover new drugs and dissect human diseases. Pharmaceutical companies have realized that novel drug targets can be identified and validated using simple model organisms and are investing more heavily in screening and research projects that use small animal models. Today, model organisms are used at all stages of drug discovery ranging from early validation of targets, in vivo efficacy, toxicological evaluation, pharmacodynamics, and identification of drug mechanism of action.