PT  - JOURNAL ARTICLE
AU  - Sigurdson, Christina J.
AU  - Joshi-Barr, Shivanjali
AU  - Bett, Cyrus
AU  - Winson, Olivia
AU  - Manco, Giuseppe
AU  - Schwarz, Petra
AU  - Rülicke, Thomas
AU  - Nilsson, K. Peter R.
AU  - Margalith, Ilan
AU  - Raeber, Alex
AU  - Peretz, David
AU  - Hornemann, Simone
AU  - Wüthrich, Kurt
AU  - Aguzzi, Adriano
TI  - Spongiform Encephalopathy in Transgenic Mice Expressing a Point Mutation in the β2–α2 Loop of the Prion Protein
AID  - 10.1523/JNEUROSCI.3504-11.2011
DP  - 2011 Sep 28
TA  - The Journal of Neuroscience
PG  - 13840--13847
VI  - 31
IP  - 39
4099  - http://www.jneurosci.org/content/31/39/13840.short
4100  - http://www.jneurosci.org/content/31/39/13840.full
SO  - J. Neurosci.2011 Sep 28; 31
AB  - Transmissible spongiform encephalopathies are fatal neurodegenerative diseases attributed to misfolding of the cellular prion protein, PrPC, into a β-sheet-rich, aggregated isoform, PrPSc. 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 β2–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 β2–α2 loop at 20°C, elicits spontaneous PrP aggregation in vivo. Transgenic mice expressing PrPD167S developed a progressive encephalopathy characterized by abundant PrP plaque formation, spongiform change, and gliosis. These results add to the evidence that the β2–α2 loop has an important role in intermolecular interactions, including that it may be a key determinant of prion protein aggregation.