Murine APP cDNA modified to have 2 mutations, Arg609 to Asp and Lys612 to Glu, was inserted into the mouse Thy1 gene, replacing a 1.5 kb fragment containing part of the sequence spanning from within exon 2 into exon 4. The thymus-specific elements in intron 3 were deleted in the construct. The construct was microinjected into fertilized 1.5-day-old pre-nuclear embryos from FVB females. RT-PCR verified expression of the transgene in the brain of heterozygotes at ~50% of endogenous App message. Line 6 was established.