Infection by ME7 prion is not modified in transgenic mice expressing the yeast chaperone Hsp104 in neurons.
The Hsp104 chaperone induces thermo-tolerance in yeast and rescues proteins trapped in aggregates. In this study, we showed that xenogenic expression of Hsp104 dramatically increased the viability of the neuronal mouse CAD cell line after exposure to heat shock. These results indicate that the Hsp104 protein confers thermo-resistance to mammalian neuronal cells, the canonical property of Hsp104 in yeast. Hsp104 also determines the prion state of prion-like proteins in yeast and to investigate whether Hsp104 expression may modify mammalian prion infection in vivo, transgenic mice with specific expression of Hsp104 in neurons were generated. Mice develop and reproduce normally, they show no detectable physical defect and may constitute valuable model for the study of aggregation-prone neuropathological disorders. Hsp104 transgenic and control littermates were infected intracerebrally with the ME7 strain of scrapie. No differences in the incubation time of the disease or in PrP(Sc) accumulation were observed between transgenic and control mice. These results suggest that the heat-shock protein Hsp104 is not efficient to modulate the multiplication of mammalian prions and/or to counteract neurodegeneration in the brain of scrapie-infected mice.
Dandoy-Dron
Françoise
F
CNRS UPR-9045, Laboratoire d'Oncologie Virale, 7 rue G. Môquet BP-8, 94801 Villejuif Cedex, France.
Bogdanova
Anna
A
Beringue
Vincent
V
Bailly
Yannick
Y
Tovey
Michael G
MG
Laude
Hubert
H
Dron
Michel
M
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000502:physiology; D005455:Fluorescent Antibody Technique / Q000379:methods; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007239:Infections; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D011328:Prions / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism; D013696:Temperature
D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D018620:PrPSc Proteins; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae