Embryonic stem (ES) cells derived from preimplantation mouse embryo provide a powerful tool for genome manipulation in mammals. The two principal genetic approaches are used to modify genomes of embryonic stem cells, which may be introduced into blastocyst to produce chimeras, and these animals transmit the genetic alteration into the next generation. One approach, targeted mutagenesis, is designed to disrupt the function of specific murine genes that are known by their homology to genes of other organisms. The other approach, gene trapping by randomly insertional mutagenesis, is designed to identify novel, developmentally regulated genes in mouse embryos. In vivo screens allow for the identification and studying of genes that are expressed either within specific tissue or in spatiotemporal patterns. As an alternative to in vivo gene study, gene expression within specific cell types may be monitored in different ES cell cultures.
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