Our ability to manipulate the genetic make-up of the mouse provides a most powerful means to perform highly controlled experiments in a mammal (1). That is, overexpressing or deleting individual genes, often at a particular time or in specific cell types, gives scientists the opportunity to determine the function of the protein encoded by the gene in vivo. When performed in the context of models of disease, such genetic manipulation enables us to dissect pathogenetic pathways more thoroughly than ever before. We simply cannot mechanistically examine humans like we can animals, particularly the mouse.
However, there is no question that humans and mice differ; how else does one explain the whiskers and tail? Nevertheless, we also share an enormous amount of genetic material and have mastered common solutions to physiologic challenges, including the development of lungs, heart, blood, and the vascular system to acquire oxygen from the atmosphere and deliver it to tissues as a primary source of energy. Furthermore, we both have an innate and adaptive immune system to handle invading pathogens. Although it is true that the structures of the lung, cells, and proteins used to carry out these parallel functions are not entirely conserved, the use of animal models to understand human disease is justified by the fact that the general strategies and the specific molecular pathways used are similar in both species.
Thus, although the issues raised in the accompanying “Con” editorial are elegant, correct, and important, they are not just cause to abandon the use of these models altogether. Rather, they should be taken under advisement as we design our experiments and interpret our results, for the trick to animal modeling lies in examining the most relevant pathways and knowing how far to take the analogy.