Acetyltransferase (AT) activity was ablated via the incorporation of engineered point mutations at the endogenous locus. The mutations substitute alanine and serine for tryptophan and tyrosine (WY(1503-1504)AS). A single loxP site remained in the intron preceding the missense mutations after the excision of floxed neo cassette used for selection. Western blot analysis indicated mutant protein was expressed at wild-type levels.