| First Author | Sigurdson CJ | Year | 2011 |
| Journal | J Neurosci | Volume | 31 |
| Issue | 39 | Pages | 13840-7 |
| PubMed ID | 21957246 | Mgi Jnum | J:176123 |
| Mgi Id | MGI:5288525 | Doi | 10.1523/JNEUROSCI.3504-11.2011 |
| Citation | Sigurdson CJ, et al. (2011) Spongiform Encephalopathy in Transgenic Mice Expressing a Point Mutation in the {beta}2-{alpha}2 Loop of the Prion Protein. J Neurosci 31(39):13840-13847 |
| abstractText | Transmissible spongiform encephalopathies are fatal neurodegenerative diseases attributed to misfolding of the cellular prion protein, PrP(C), into a beta-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 beta2-alpha2 loop in the NMR structure at pH 4.5 and 20 degrees 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 beta2-alpha2 loop at 20 degrees 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 beta2-alpha2 loop has an important role in intermolecular interactions, including that it may be a key determinant of prion protein aggregation. |
