Related Experiment Video
Updated: Feb 25, 2026
Monitoring Immune Cells Trafficking Fluorescent Prion Rods Hours after Intraperitoneal Infection
Published on: November 19, 2010
Correlation of cellular factors and differential scrapie prion permissiveness in ovine microglia
Kelcey D Dinkel1, David A Schneider2, Juan F Muñoz-Gutiérrez3
1Veterinary Microbiology and Pathology, Washington State University, PO Box 647040, Pullman, WA, 99164-7040, United States.
Abstract:
Prion diseases are fatal neurodegenerative disorders by which the native cellular prion protein (PrPC) is misfolded into an accumulating, disease-associated isoform (PrPD). To improve the understanding of prion pathogenesis and develop effective treatments, it is essential to elucidate factors contributing to cellular permissiveness. We previously isolated five clones from an immortalized subline of ovine microglia, two of which had demonstrated differential permissiveness to a natural isolate of sheep scrapie and distinct transcriptomic profiles. To more robustly identify factors contributing to this activity, relative permissiveness, cell proliferation, selected gene transcript level, and matrix metalloproteinase 2 (MMP2) activity were compared amongst all five clones. Differences in cell proliferation were not detected between clones; however, significant correlations were identified between relative permissiveness and genes associated with cell growth (i.e., RARRES1 and PTN), protein degradation (i.e., CTSB and SQSTM1), and heparin binding (i.e., SEPP1). MMP2 activity varied amongst clones, but did not correlate with permissiveness. These associations support the contribution of cell division and protein degradation on the permissiveness of cultured ovine microglia to PrPD.
Insights
Understanding prion diseases requires identifying factors that make cells susceptible. This study found that cell growth and protein degradation genes correlate with ovine microglia
Area of Science:
- Neurodegenerative diseases
- Prion biology
- Cellular pathogenesis
Background:
- Prion diseases involve misfolding of cellular prion protein (PrPC) into a disease-associated form (PrPD).
- Understanding cellular permissiveness is key to developing treatments for prion disorders.
- Previous work identified differential permissiveness in ovine microglia clones.
Purpose of the Study:
- To identify factors contributing to the permissiveness of ovine microglia to prion disease.
- To compare cell proliferation, gene expression, and MMP2 activity across five ovine microglia clones.
Main Methods:
- Cultured five immortalized ovine microglia clones.
- Assessed relative permissiveness to sheep scrapie.
- Compared cell proliferation, transcript levels of selected genes, and matrix metalloproteinase 2 (MMP2) activity.
Main Results:
- No significant differences in cell proliferation were observed among clones.
- Relative permissiveness correlated with genes involved in cell growth (RARRES1, PTN), protein degradation (CTSB, SQSTM1), and heparin binding (SEPP1).
- MMP2 activity varied but did not correlate with permissiveness.
Conclusions:
- Cell growth and protein degradation pathways are associated with ovine microglia permissiveness to prion disease.
- These findings advance understanding of prion pathogenesis mechanisms.
- Identified specific genes that may influence susceptibility to prion infection in microglia.
