Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans.
Transgenic Caenorhabditis elegans nematodes have been engineered to express potentially amyloidic human proteins. These animals contain constructs in which the muscle-specific unc-54 promoter/enhancer of C. elegans drives the expression of the appropriate coding regions derived from human cDNA clones. Animals containing constructs expressing the 42-amino acid beta-amyloid peptide (derived from human amyloid precursor protein cDNA) produce muscle-specific deposits immunoreactive with anti-beta-amyloid polyclonal and monoclonal antibodies. A subset of these deposits also bind the amyloid-specific dye thioflavin S, indicating that these deposits have the tinctural characteristics of classic amyloid. Co-expression of beta-peptide and transthyretin, a protein implicated in preventing the formation of insoluble beta-amyloid, leads to a dramatic reduction in the number of dye-reactive deposits. These results suggest that this invertebrate model may be useful for in vivo investigation of factors that modulate amyloid formation.
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Department of Biological Sciences, University of Denver, CO 80208, USA.
D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D052160:Benzothiazoles; D002107:Caenorhabditis / Q000378:metabolism*; D002678:Chimera; D017931:DNA Primers; D000939:Epitopes / Q000032:analysis; D005456:Fluorescent Dyes / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008969:Molecular Sequence Data; D011228:Prealbumin / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D015183:Restriction Mapping; D013844:Thiazoles / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D052160:Benzothiazoles; D017931:DNA Primers; D000939:Epitopes; D005456:Fluorescent Dyes; D011228:Prealbumin; D011993:Recombinant Fusion Proteins; D013844:Thiazoles; C009462:thioflavin T