Spongiform encephalopathy in transgenic mice expressing a point mutation in the ß2-α2 loop of the prion protein.
J Neurosci
; 31(39): 13840-7, 2011 Sep 28.
Article
in En
| MEDLINE
| ID: mdl-21957246
ABSTRACT
Transmissible spongiform encephalopathies are fatal neurodegenerative diseases attributed to misfolding of the cellular prion protein, PrP(C), into a ß-sheet-rich, aggregated isoform, PrP(Sc). We previously found that expression of mouse PrP with the two amino acid substitutions S170N and N174T, which result in high structural order of the ß2-α2 loop in the NMR structure at pH 4.5 and 20°C, caused transmissible de novo prion disease in transgenic mice. Here we report that expression of mouse PrP with the single-residue substitution D167S, which also results in a structurally well ordered ß2-α2 loop at 20°C, elicits spontaneous PrP aggregation in vivo. Transgenic mice expressing PrP(D167S) developed a progressive encephalopathy characterized by abundant PrP plaque formation, spongiform change, and gliosis. These results add to the evidence that the ß2-α2 loop has an important role in intermolecular interactions, including that it may be a key determinant of prion protein aggregation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prion Diseases
/
Point Mutation
/
PrPC Proteins
Type of study:
Diagnostic_studies
Limits:
Animals
Language:
En
Journal:
J Neurosci
Year:
2011
Document type:
Article
Affiliation country:
United States