Exons 16 and 17 were replaced with a loxP site, a truncated exon 16 with a BACE cleavage site at K670M671 followed by a stop codon, an FRT-flanked neo cassette with a 3' loxP site, a modified exon 16 with the Swedish mutation K595N/M596L (APP695) and three additional mutations (G601R, F606Y, R609H) to humanize the sequence, and a modified exon 17 with the Arctic mutation E618G, London mutation V642I, silent mutation on G621S622 (GGTTCG to GGATCC) to create a BamHI site, and a frameshift mutation starting at I656H657H658 (ATC CAT CAT to ATC ATC AT) that results in a stop codon 30 bp after the frameshift side such that there are 10 resides behind I656. Cre-mediated recombination removed the truncated exon 16 and the neo cassette.