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Nature 336, 348-352 (24 November 1988) | doi:10.1038/336348a0; Accepted 14 October 1988

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

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