Identification of a novel alternative splicing isoform of human amyloid precursor protein gene, APP639.
Senile plaques, neurofibrillary tangles and amyloid-laden cerebral vessels are characteristic features in the brains of individuals with Alzheimer's disease (AD). The principal component of amyloid in senile plaque and amyloid-laden cerebral vessels is beta-amyloid (Abeta), a peptide proteolytically derived from a large amyloid precursor protein (APP). To date, several alternatively spliced human APP transcripts have been described. Here, we report the identification of a novel alternative splicing isoform of the human APP gene, APP639, which excludes exon 2 as well as exons 7 and 8. RT-PCR and Southern blot analysis show that APP639 mRNA is expressed in many human fetal tissues. In contrast, the APP639 transcript is hardly detected in the aged human cerebral cortex from both pathologically confirmed sporadic AD cases and nondemented controls. However, APP639 mRNA exists in the adult human liver. Western blot analysis shows that the protein product produced from the APP639 cDNA could be recognized by the APP antibody, and it does lack the exon 2 coding region. These results suggest that APP639, a novel alternative splicing isoform of human APP gene, does exist in human tissues in vivo.
Tang
Ke
K
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Wang
Chen
C
Shen
Chengyong
C
Sheng
Shuli
S
Ravid
Rivka
R
Jing
Naihe
N
D000328:Adult; D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D015139:Blotting, Southern; D015153:Blotting, Western; D002460:Cell Line; D015342:DNA Probes; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007536:Isomerism; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D015342:DNA Probes; D018076:DNA, Complementary; D011993:Recombinant Fusion Proteins