Molecular cloning of the promoter of the gene encoding the Rhesus monkey beta-amyloid precursor protein: structural characterization and a comparative study with other species.

Abnormal regulation of transcription of the beta-amyloid precursor protein (betaAPP) gene is implicated in the pathogenesis of Alzheimer's disease (AD). We have examined 17- kb genomic region which contains the 5'-flanking region (promoter), first exon and on of the betaAPP gene of the Rhesus monkey (rhbetaAPP). A predominant scription start site was tified 146 bp upstream of the translation initiation codon. Sequencing 5848 bp of 5'-flanking revealed the presence of multiple near consensus sequences for binding potential transcriptional regulatory factors, such as activator proteins (AP-1, AP-2), an apolipoprotein E-B1 element, estrogen-responsive element, heat shock element and NF-kappaB. The sequence of the rhbetaAPP promoter also contains several sites for the binding of proteins that serve as signal transducers and activators of transcription (STAT1) (GAS). The rhbetaAPP promoter is highly homologous to the human promoter, but less homologous to the rodents. The homology between human and Rhesus monkey of the further upstream region gradually decreased over its length. A region of 270 bp of the human betaAPP promoter is missing from the Rhesus monkey promoter. Structural analysis of the promoter suggests that it contains characteristics of inducible genes and sites for regulated activity by various transcription factors.