Porcine APP cDNAs: Molecular cloning and characterization, expression analysis, chromosomal localization and SNP analysis

Abstract

The human amyloid precursor protein (APP) is the precursor of Aβ, a peptide with the potential to create amyloid plaques in neurons. Mutations in the human APP gene are associated with the familial form of Alzheimer's disease. In addition, differential expression of three alternative pre-mRNA APP splicing variants of 695, 751, and 770 amino acids is linked to the pathogenesis. In this study, two novel transcript variants of porcine APP have been identified, producing isoforms of 695 and 751 amino acids, respectively. These are highly homologous to APP orthologues from other vertebrate species. Expression analyses revealed that the gene is expressed in all 30 examined porcine tissues and in a selected subset of these, differential representation of the three major APP transcript variants was observed. The APP isoform of 770 amino acids clearly predominates in non-neuronal tissues while in porcine cerebellum, the APP isoforms of 695 and 770 amino acids are expressed at equivalent levels. Employing a somatic cell hybrid panel, the APP gene was mapped to porcine chromosome 13 in either the 13q41 or 13q46–q49 region. A large pig population was screened for single nucleotide polymorphisms (SNPs) in APP exon 17 and flanking intron sequences. No missense mutations were detected; however, the allele frequencies of two silent mutations and two intron polymorphisms varied significantly among breeds.