Expression of the gene encoding the beta-amyloid precursor protein APP in Xenopus laevis.
The beta-amyloid precursor protein APP is generally accepted to be directly or indirectly involved in the neurodegenerative disorder Alzheimer's disease and has been extensively studied in a number of mammalian systems. Its normal function remains, however, still elusive. We have used the clawed toad, Xenopus laevis, to study the first non-mammalian APP protein. Screening of a Xenopus laevis intermediate pituitary cDNA library led to the identification of two structurally different APP gene transcripts presumably resulting from duplicated genes. Sequence comparison between the Xenopus and human APP proteins revealed at the amino acid sequence level an identity of 92%. Both Xenopus genes were found to be expressed in all tissues examined, but their expression levels differed among tissues. In addition, as in mammals, alternative splicing was observed and the alternatively spliced APP(695) mRNA variant was expressed predominantly in the brain and the oocyte, while the longer isoforms (APP(751-770)) were predominant in the other tissues examined. Of special interest is the finding that, like human but unlike mouse or rat beta-amyloid (Abeta), the Xenopus peptide contains all amino acid residues implicated in amyloidogenesis. We conclude that Xenopus APP mRNA is ubiquitously expressed and alternatively spliced, and that the highly conserved Xenopus APP protein contains an Abeta peptide with amyloidogenic potency.
van den Hurk
W H
WH
Department of Molecular Animal Physiology, University of Nijmegen, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands.
Bloemen
M
M
Martens
G J
GJ
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D018076:DNA, Complementary / Q000235:genetics; D004285:Dogs; D019143:Evolution, Molecular; D020440:Gene Duplication; D020869:Gene Expression Profiling; D015723:Gene Library; D005796:Genes; D006168:Guinea Pigs; D006801:Humans; D008322:Mammals / Q000235:genetics; D051379:Mice; D023421:Models, Animal; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010904:Pituitary Gland, Posterior / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D051381:Rats; D016415:Sequence Alignment; D017385:Sequence Homology; D012756:Sheep; D013552:Swine; D001503:Ursidae; D014982:Xenopus laevis / Q000235:genetics* / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D018076:DNA, Complementary; D020033:Protein Isoforms; D012333:RNA, Messenger