The targeting was designed to alter the DNA sequence of codon 148 in exon 3 from CTA to ATG creating a leucine-to-methionine amino acids substitution (L148M) and insert a loxP-flanked PGK-neo selection cassette in intron 3. The substitution is analogous to the human Val<158>Met mutation. Cre-mediated recombination removed the floxed neo cassette. Immunoblot analysis indicats that both soluble and membrane bound protein isoforms are reduced in all brain regions.