Cytoplasmic expression of mouse prion protein causes severe toxicity in Caenorhabditis elegans.
To test if Caenorhabditis elegans could be established as a model organism for prion study, we created transgenic C. elegans expressing the cytosolic form of the mouse prion protein, MoPrP(23-231), which lacks the N-terminal signal sequence and the C-terminal glycosylphosphatidylinisotol (GPI) anchor site. We report here that transgenic worms expressing MoPrP(23-231)-CFP exhibited a wide range of distinct phenotypes: from normal growth and development, reduced mobility and development delay, complete paralysis and development arrest, to embryonic lethality. Similar levels of MoPrP(23-231)-CFP were produced in animals exhibiting these distinct phenotypes, suggesting that MoPrP(23-231)-CFP might have misfolded into distinct toxic species. In combining with the observation that mutations in PrP that affect prion pathogenesis also affect the toxic phenotypes in C. elegans, we conclude that the prion protein-folding mechanism is similar in mammals and C. elegans. Thus, C. elegans can be a useful model organism for prion research.
Park
Kyung-Won
KW
Department of Molecular Pharmacology and Biological Chemistry, The Feinberg School of Medicine, Northwestern University, Searle 5-474, MC S205, 320 East Superior Street, Chicago, IL 60611, USA.
Li
Liming
L
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D003593:Cytoplasm / Q000378:metabolism; D003902:Detergents / Q000737:chemistry; D004195:Disease Models, Animal; D019286:Endopeptidase K / Q000737:chemistry; D051379:Mice; D032342:Muscle Cells / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D012521:Sarcosine / Q000031:analogs & derivatives / Q000737:chemistry; D012995:Solubility
D003902:Detergents; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; C025231:sarkosyl; D019286:Endopeptidase K; D012521:Sarcosine