NR AFHY
AU Heppner,F.L.; Musahl,C.; Arrighi,I.; Klein,M.A.; Rülicke,T.; Oesch,B.; Zinkernagel,R.M.; Kalinke,U.; Aguzzi,A.
TI Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies
QU Science 2001 Oct 5; 294(5540): 178-82
PT journal article
AB Variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy are initiated by extracerebral exposure to prions. Although prion transmission from extracerebral sites to the brain represents a potential target for prophylaxis, attempts at vaccination have been limited by the poor immunogenicity of prion proteins. To circumvent this, we expressed an anti-prion protein (anti-PrP) mu chain in Prnp(o/o) mice. Transgenic mice developed sustained anti-PrP titers, which were not suppressed by introduction of Prnp+ alleles. Transgene expression prevented pathogenesis of prions introduced by intraperitoneal injection in the spleen and brain. Expression of endogenous PrP (PrPc) in the spleen and brain was unaffected, suggesting that immunity was responsible for protection. This indicates the feasibility of immunological inhibition of prion disease in vivo.
MH Amyloid/genetics; Animal; Antibodies/blood/*immunology; B-Lymphocytes/immunology; Blotting, Western; Brain Chemistry; Cell Separation; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Immunoglobulin M/blood/immunology; Immunoglobulins, mu-Chain/blood/immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; PrPc Proteins/genetics; PrPsc Proteins/analysis/*immunology; Prions/genetics/*immunology; Protein Precursors/genetics; Scrapie/*prevention & control; Spleen/chemistry/immunology; Support, Non-U.S. Gov't
AD Institute of Neuropathology, Institute of Laboratory Animal Science, Institute of Experimental Immunology, University Hospital Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
SP englisch
PO USA