The coding sequence of amyloid-beta precursor protein APP contains a neural-specific promoter element.
The amyloid-beta precursor protein APP is generally accepted to be involved in the pathology of Alzheimer's disease. Since its physiological role is still unclear, we decided to study the function of APP via stable transgenesis in the amphibian Xenopus laevis. However, the application of constructs encoding (mutant) APP fused to the C-terminus of the green fluorescent protein GFP (GFP-APP), and harboring a tissue-specific or an inducible gene promoter did not result in transgene expression of APP in neuronal and neuroendocrine cells. Surprisingly, a construct encoding either Xenopus or human APP fused to the N-terminus of GFP (APP-GFP) gave fluorescence throughout the whole brain of the tadpole, despite the fact that a proopiomelanocortin gene promoter was used to target transgene expression specifically to the intermediate pituitary cells. Detailed analysis with deletion mutants revealed the presence of a neural-specific, transcriptionally active DNA element within the 3'-end of the APP-coding sequence that gave rise to an aberrant transcript and protein in the APP-GFP transgenic animals. The DNA element appears to prevent proper APP transgene expression in Xenopus neuronal and neuroendocrine cells. Thus, the coding sequences of Xenopus and human APP contain a neural-specific promoter element, the physiological significance of which is at present unclear.
Collin
Rob W J
RW
Department of Molecular Animal Physiology, Nijmegen Center for Molecular Life Sciences, NCMLS, and Institute for Neuroscience, Radboud University Nijmegen, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands.
Martens
Gerard J M
GJ
D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D004318:Doxycycline / Q000494:pharmacology; D004625:Embryo, Nonmammalian; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005815:Genetic Code; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D014162:Transfection; D014982:Xenopus laevis
D016564:Amyloid beta-Protein Precursor; D049452:Green Fluorescent Proteins; D009074:Melanocyte-Stimulating Hormones; D004318:Doxycycline