gms | German Medical Science

The ability to modify the mouse genome at predetermined sites by homologous recombination in embryonic stem cells has greatly advanced our understanding of mammalian gene function. This method introduces a permanent genetic alteration into the mouse germ line and is being used, for instance, to generate “global” gene knockouts that are present in every cell of the animal. In addition, recent advances allow conditional, i.e. spatio-temporally controlled, genome manipulations in somatic cells of the mouse. Using the Cre/lox site-specific recombination system it is now possible to activate or inactivate a selected gene, at a chosen time, in a specific cell type of living mice, offering unprecedented possibilities for generating animal models for human diseases. We have developed an inducible Cre/lox system that can be switched on by administration of the synthetic drug tamoxifen (the so-called tamoxifen system) and have used this technique to study proliferative disorders such as atherosclerosis. Likewise, a new generation of mouse tumor models became reality with the ability to induce somatic mutations of selected oncogenes or tumor suppressor genes in a temporally defined and tissue-specific manner. The potentials and limitations of these new technological developments will be discussed, with a focus on modelling cancer in mice.