Tg(APPSwLon)96Btla

A 650 kb YAC transgene containing the entire human amyloid beta (A4) precursor protein gene and approximately 250 kb of flanking sequence was altered to include the Familial Alzheimer's Disease- (FAD-) associated "Swedish" double mutation, APPK670N/M671L, and the "London" mutation, APPV717I. RT-PCR analysis shows hemizygous mice express the mutant human and endogenous mouse APP mRNA at similar levels in brain and peripheral tissues; levels of the most common alternative splice variants (encoding human APP-695, -751 and -770) parallel those of the endogenous mouse transcripts. Levels of total amyloid-beta and of longer amyloid-beta peptides (species terminating at amino acids 42/43) are higher than in wildtype mice, but not as high as in a similar strain carrying only the APPK670N/M671L "Swedish" mutant transgene. (J:42613)