Fig. 1

Generation of OSK-KI mice. (a) Mice were generated by knocking-in the Osaka mutation (deletion of codon 693) into endogenous mouse APP by homologous recombination in embryonic stem cells. (i) Mouse APP contains 18 exons (black boxes), and Aβ is coded in exons 16 and 17. (ii) The targeting vector contains mouse APP exon 16, mutant exon 17 with the deletion (white box), and the neomycin-resistance gene driven by the phosphoglycerate kinase 1 promoter (PGK-neo). (iii) Homologous recombinants were determined by Southern blotting using the 5' and 3' probes. (b) Expression levels of APP in homozygous, heterozygous, and non-KI mice. Brain homogenates at 24 months were subjected to Western blot with antibodies to APP C-terminus (C40) and actin. Each bar represents the mean ± SEM (n = 4 for each group). AU, arbitrary unit