Genetic knockouts in mice: an update.

Gene disruption technology in mammals, by homologous recombination in embryonic stem cells, is a powerful method to manipulate the mouse germ line. In the past decade it has produced a wealth of knowledge concerning neuronal development, neurodegenerative disorders and the roles of oncogenes, Hox genes and growth factors during development. A surprising variety of genes, however, have given unexpected and disappointing results. A gene/function redundancy theory proposed by many investigators to explain the unexpected results has been supported in certain cases by the generation of double knockout mice. Modification of the basic technology now allows the investigators to carry out a variety of manipulations including conditional or tissue-specific knockouts. This may provide a better opportunity in the future for the gene therapy approach to correct the genetic disorder.