Knock-in and knock-out. Transgenes, Development and Disease: A Keystone Symposium sponsored by Genentech and Immunex, Tamarron, CO, USA, January 12-18, 1991.

The meeting clearly reflected the recent rapid and staggering progress in the use of transgenic mice. Being able to manipulate single units of genetic information in their natural position in a cell genome and to examine the results of that manipulation in the background of a terminally differentiated organism has been an outstanding achievement on the road toward a deeper and generalizable understanding of complex life forms. However, there are many examples of genetic diseases in humans (for instance, Lesh-Nyhan syndrome, Duchenne muscular dystrophy, phenylketonuria) whose genotypic "equivalent" in transgenic mice results in very different phenotypes or no phenotypic changes at all. Mice are clearly not human beings. Why not? No doubt, we will find out!