The cDNA encoding human APOE isoform 4 carrying the substitution C112R was mutated at residue 28 from leucine to proline (L28P) by site-specific mutagenesis. The cDNA was cloned into a vector downstream of the rat glial fibrillary acid protein (Gfap) promoter and regulatory elements and upstream of the human beta-globin splice and polyadenylation sites. The linearized construct was injected into the male pronuclei of B6D2F1 zygotes. (J:100970)