EXPRESSION OF HUMAN BETA-AMYLOID PEPTIDE IN TRANSGENIC CAENORHABDITIS-ELEGANS

Transgenic Caenorhabditis elegans nematodes have been engineered to ex press potentially amyloidic human proteins. These animals contain cons tructs in which the muscle-specific unc-54 promoter/enhancer of C. ele gans drives the expression of the appropriate coding regions derived f rom 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 an ti-beta-amyloid polyclonal and monoclonal antibodies. A subset of thes e deposits also bind the amyloid-specific dye thioflavin S, indicating that these deposits have the tinctural characteristics of classic amy loid, Coexpression of beta-peptide and transthyretin, a protein implic ated in preventing the formation of insoluble beta-amyloid, leads to a dramatic reduction in the number of dye-reactive deposits. These resu lts suggest that this invertebrate model may be useful for in vivo inv estigation of factors that modulate amyloid formation.