Prion Strain Discrimination Based on Rapid In Vivo Amplification and Analysis by the Cell Panel Assay

Abstract

Prion strain identification has been hitherto achieved using time-consuming incubation time determinations in one or more mouse lines and elaborate neuropathological assessment. In the present work, we make a detailed study of the properties of PrP-overproducing Tga20 mice. We show that in these mice the four prion strains examined are rapidly and faithfully amplified and can subsequently be discriminated by a cell-based procedure, the Cell Panel Assay.

A Proposed Mechanism for the Promotion of Prion Conversion Involving a Strictly Conserved Tyrosine Residue in the β2-α2 Loop of PrPC

“…Two mouse prion strains, RML and 22L, were used to seed conversion of PrP C . RML and 22L strains are distinguished by their differing incubation period and brain lesion distribution in mice (46).…”

Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins

“…In all cases, 3rd-passage incubation periods for animals injected with 1% brain homogenates of TSE-positive 2nd-passage inocula were dramatically reduced (Table 1). With the exception of tg44 ϩ/ϩ mice, incubation periods converged on values longer than those associated with typical mouse scrapie in the respective mouse strains (13,15,29). Remarkably, the average incubation period for the 2nd passage of the D013 agent in tg44 ϩ/ϩ mice (234 Ϯ 19 dpi) was approximately 100 days faster than that for primary passage of 22L or Chandler in the same mouse strain (13).…”

Profoundly different prion diseases in knock-in mice carrying single PrP codon substitutions associated with human diseases

“…However, they are prone to variable expression levels and patterns, depending on copy number and genome integration site. Indeed, one of the most popular vectors for modeling neurodegenerative diseases, a Prnp promoter fragment lacking an intron that contains regulatory information, is highly prone to integration effects (23,33,34). Even very large vectors such as those created by BACs can have variable spatial expression patterns (35).…”