Potential for genetic manipulation of mammals.

The development of a new mammalian genetics in which specifically designed gene alterations of pre-existing endogenous genetic loci may be achieved via tissue culture of stem cells is described. At present this technology is rapidly emerging for mice by gene targeting in cultured embryonic stem cells, isolation of the desired cell clone and re-constitution of germ-line chimaeric animals. Results to date and strategies for gene targeting and isolation of the required cell clones are discussed. This new genetic technology is likely to have a major impact both in genetic studies and, especially if it can be extended to larger mammalian species, in practical applications.