Change in the molecular properties of CH1641 prions after transmission to wild‐type mice: Evidence for a single strain

• Published in: Neuropathology and applied neurobiology 2024-02, Vol.50 (1), p.e12963-n/a
• Main Authors: Keulen, Lucien J. M., Dolstra, Corry H., Vries, Ruth Bossers‐de, Bossers, Alex, Jacobs, Jorg G., Baron, Thierry, Torres, Juan Maria, Langeveld, Jan P. M.
• Format: Article
• Language: English
• Subjects: Animals; Cattle; classical scrapie; Life Sciences; Mice; Mice, Transgenic; Prion Proteins - genetics; Prions - metabolism; protease resistant prion; PrP protein; PrPSc; PrPSc Proteins - metabolism; Scrapie - metabolism; Sheep; strain typing; transgenic mice
• ISSN: 0305-1846; 1365-2990
• DOI: 10.1111/nan.12963

Aim CH1641 was discovered in 1970 as a scrapie isolate that was unlike all other classical strains of scrapie isolated so far. We performed bio‐assays of CH1641 in mice in order to further characterise this specific isolate. Methods We inoculated the original CH1641 isolate into ovine and bovine prion protein (PrP) transgenic mice as well as wild‐type mice. In addition, we performed cross‐ and back passages between the various mouse lines to examine if one identical prion strain was isolated in all mouse lines or whether multiple prion strains exist in CH1641. Results We report the first successful transmission of CH1641 to wild‐type RIII mice and via RIII mice to wild‐type VM mice. Unexpectedly, analysis of the protease‐resistant prion protein (PrPres) in wild‐type mice showed a classical scrapie banding pattern differing from the banding pattern of the original CH1641 isolate. Cross‐ and back passages of CH1641 between the various mouse lines confirmed that the same prion strain had been isolated in all mouse lines. Conclusions The CH1641 isolate consists of a single prion strain but its molecular banding pattern of PrPres differs between wild‐type mice and PrP transgenic mice. Consequently, molecular banding patterns of PrPres should be used with caution in strain typing since they do not solely depend on the properties of the prion strain but also on the host prion protein. The scrapie isolate CH1641 was transmitted to various mouse lines and PrPSc depositions at the level of the thalamus were immunostained. CH1641 passaged through Tg338 (A), Tg110 (B), RIII (C) and VM (D) mice was cross passaged to Tg59 mice. All PrPSc profiles at the level of the thalamus were similar to the PrPSc profile of the homologous passage of CH1641 in Tg59 mice (centre) indicating that the same strain was isolated in all mouse lines.