Patent ID: 7638334

Claim:
A method of introducing a locus specific targeting fragment into the genome of a cell in vitro through homologous recombination comprising: inhibiting endogenous mismatch repair in cells of a cell population by introducing into said cells a polynucleotide comprising a dominant negative form of the human PMS2 gene, wherein the dominant negative form of said human PMS2 gene is PMS2-134, PMSR2, or PMSR3 and wherein said polynucleotide is expressed, thereby generating mismatch repair-inhibited cells; contacting said mismatch repair-inhibited cells with a locus specific targeting fragment, wherein said locus specific targeting fragment is a polynucleotide comprising at least one promoter, a sequence encoding a selectable marker, and 5′ and 3′ flanking regions of about 20 to about 120 nucleotides; wherein said 5′ and 3′ flanking regions are homologous to a selected portion of the genome of said cells; and wherein said locus specific targeting fragment integrates into the genome of said cells by homologous recombination; and selecting a cell comprising said locus specific targeting fragment.