GENE-TARGETING AND THE P53 TUMOR-SUPPRESSOR GENE

Gene-targeting techniques are now frequently applied to embryonic stem (ES) cells to introduce mutations of endogenous genes in mice. Modifi cations introduced into tumor-suppressor genes by this technology have produced mice and cell lines with unique tumorigenic and growth chara cteristics, respectively. A number of strategies have been developed t o enhance the efficiency of homologous recombination between targeting vectors and endogenous genes. This review describes recent advances i n the techniques used to construct mice with a variety of genetic alte rations. In addition, an application of gene-targeting is illustrated in the study of a class of genes with tumor-suppressor function. Recen t findings from experiments using gene targeted mice to study the p53 tumor-suppresser gene are discussed and the potential of gene-targetin g for the discovery and study of novel tumor-suppressor genes are expl ored.