The molecular revolution in science has had an enormous impact on animal facilities- Research shifted from studies in living animals to studies in human tissues and cultured cells, and, most recently to the production of "designer mice.' These mice arc answering important scientific questions, refining hazard evaluations, and changing the nature of our animal facilities as researchers clamor for increasingly more sophisticated models of disease. We are all familiar with mutant mice and their importance to research. Nude and SCID mice, for example, are used in tissue transplantation and immunology studies. Produced by chance events, these mice are being preserved for their value to science. In contrast, the intentional insertion or activation of genetic material (transgenic mice), or the intentional inactivation of a specific gene or genes (knockout mice) produces most new mutant mice. The genetic changes in these mice are the result of the experimental design, rather than chance. For example, investigators have produced mice with defects in the gene that causes cystic fibrosis in humans. The technology has become sophisticated enough that transgene expression may be tied to tissue-specific functions and, therefore, present only in those specific tissues. Mice can be constructed so that although the gene is inactivated (knockout mice), the gene can be turned back on at a predetermined point in mouse growth or development, or in association with other specific events, such as changes associated with the development of cancer (these are called "knock-in" mice. Finally, we can construct mice with more than one transgene or with the loss of function of more than one gene. This ability permits us to study the effects of multiple genes on the development of disease, especially cancer, which is typically considered a consequence of defects in multiple genes. In toxicology research, transgenic and knockout mice are of value for hazard evaluation, mechanistic studies, and studies of therapeutic intervention in genetic disease. The use of transgenic and knockout mice in toxicology is the subject of several extensive reviews.
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