A loxP site was inserted upstream of exon 14 and a cassette, consisting of a loxP511
site, a linker, an inverted loxP site, an inverted exon 14 containing a G1849T mutation, an inverted loxP511 site, and an FRT flanked neo selection cassette, was inserted downstream of exon 14 via homologous recombination. The neo cassette was removed by flp mediated recombination. Cre mediated recombination results in the removal of the endogenous exon 14 and the inversion of the mutated exon 14. The G1849T mutation results in a V617F substitution.