Knockout Mice and Steroid Receptor Research

The development of techniques that allow defined alterations of the mammalian genome have dramatically increased the possibilities for elucidating functions of specific genes in the context of a whole organism. Although some of these techniques have been applied to several mammalian species, it is primarily the mouse that is the subject for these types of experiments. The first technique developed in this field was transgene technology, involving the incorporation of new copies of a gene into the genome of the host organism, and was successfully performed for the first time in 1980 (1 ,2 ). The other technique used to alter the mouse genome is referred to as “gene-targeting technology,” or more popularly, “knockout technology.” This technology involves homologous recombination in embryonic stem cells (ES cells) and was developed during the same decade (3 ,15 ) Gene targeting in ES cells has allowed scientists to perform studies of gene function in a way that has never been possible before. This review focuses on knockout technology, but also includes some background about transgenesis, because of its relevance for conditional knockouts. For more detailed information regarding establishment of transgenic mice, see ref. 16.