cDNA encoding the human PSEN1 sequence containing the A246E mutation was ligated into the mouse Thy1 gene. In the final construct, coding sequences and introns 1 and 2 of the Thy1 gene are replaced by the mutant PSEN1 sequence, with the 5' neuron-specific control sequences of Thy1 intact. Linearized minigenes are microinjected into prenuclear FVB/N embryos. Mutant PSEN1 mRNA and protein are detected in total brain extracts by Northern and Western blotting, respectively.