The targeting vector was used to introduce the human R684H, F681Y, G676R and KM670/671NL (Swedish) mutations into to exon 16. An FRT-flanked PGK-neomycin cassette (in reverse transcriptional orientation), and an F3-flanked PGK-hygromycin cassette (in reverse transcriptional orientation) is placed in intron 16, and the E693G (Artic) and T714I (Austrian) mutations are introduced to exon 17. Flpe-mediated recombination removed the FRT-flanked neomycin and hygromycin cassettes. (J:299724)