Neuron-specific splicing of the Alzheimer amyloid precursor protein gene in a mini-gene system.
Several forms of Alzheimer amyloid precursor protein (APP) mRNA are generated by alternative splicing. Among them, the APP695 mRNA skipping the exon 7 and 8 is expressed specifically in neurons, suggesting that this alternative splicing is regulated in a neuron-specific manner. As the first step for investigating the mechanism of the neuron-specific splicing, a mini-gene system was developed, in which mini-APP genes consisting of the exon 6, 7, 8, 9 and their flanking regions were introduced into neuronal and nonneuronal cultured cell lines to see their expression profiles. In the system the exon 7 and 8 of the mini-gene were significantly skipped in the neuronal cell, and the deletion study indicated that cis-acting elements for skipping the exons existed in the corresponding skipped-exon and its flanking regions. A small deletion upstream of the exon 8 suppressed the skipping of the exon 8 in the neuronal cell, suggesting that one of the regulatory sequence(s) for the exon skipping exists in a small region upstream of the skipped exon.
Yamada
T
T
Department of Neurology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Goto
I
I
Sakaki
Y
Y
D017398:Alternative Splicing; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics*; D001483:Base Sequence; D005091:Exons; D005796:Genes; D005910:Glioma; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D012333:RNA, Messenger / Q000096:biosynthesis*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016564:Amyloid beta-Protein Precursor; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger