Two transgenes inserted at a single locus in Chromosome 9 between Arpp21 and Pdcd6ip. Each transgene is controlled by the mouse prion promoter and contains a cDNA sequence. In one transgene the cDNA encodes a chimeric amyloid beta (A4) precursor protein (APPswe). In the second transgene the cDNA encodes the "DeltaE9" mutation of human presenilin 1. The DeltaE9 mutation of the human presenilin 1 gene is a deletion of exon 9 and corresponds to a form of early-onset Alzheimer's disease. The amyloid beta precursor protein coding sequences were altered by replacing mouse sequence encoding three amino acids of the A-beta domain with the human coding sequence for these residues. The chimeric amyloid beta (A4) precursor protein sequence was then further modified to encode the Swedish mutations K595N/M596L found in human. Both the transgenic peptide and holoprotein are detected by Signet Laboratories' monoclonal 6E10 antibody, which is specific for human sequence within this region. Human presenilin protein, which in high levels displaces detectable endogenous mouse protein, is immunodetected in the double transgenic mouse in whole brain protein homogenates. Human amyloid precursor protein is also immunodetected in these mice in whole brain protein homogenates. Transgene insertion occurred on Chr 9, causing a 1 bp duplication. (J:78664, J:227541)
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