A wloxP site was inserted upstream of exon 16. An inverted segment that contained an mloxP flanked, modified exon 16 with an upstream wloxP site and an FRT-flanked neo cassette was inserted downstream of exon 16. The modified exon 16 contains an C to T transition that results in an glutamic acid to lysine at position 846 (E846K, equivalent to a mutation found in Noonan syndrome (NS) patients). Flp-mediated recombination removed the neo cassette. Cre-mediated recombination rearranged the modified exon 16 into correct orientation and removed the endogenous exon 16. (J:171873)