An expression cassette, containing a beta-galactosidase gene adjoined to an IRES as well as a neomycin resistance gene adjoined to a MC1 promoter, was inserted 2 nucleotides downstream of the start codon. The deleted sequence extended through the end of exon 1, a total of 165 nucleotides. Beta-secretase activity was undetected in brain homogenates and extracts of cortical cell cultures derived from homozygous mutant animals. (J:77414)