Nature 336, 348 - 352 (24 November 1988); doi:10.1038/336348a0

Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes

Suzanne L. Mansour, Kirk R. Thomas & Mario R. Capecchi

Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA

Gene targeting—homologous recombination of DNA sequences residing in the chromosome with newly introduced DNA sequences—in mouse embryo-derived stem cells promises to provide a means to generate mice of any desired genotype. We describe a positive and negative selection procedure that enriches 2,000-fold for those cells that contain a targeted mutation. The procedure was applied to the isolation of hprt^- and int-2^- mutants, but it should be applicable to any gene

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