Related Experiment Video
Updated: Aug 8, 2026
Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Cellular isoform of the prion protein PrPc in human intestinal cell lines: genetic polymorphism at codon 129, mRNA
Nicolas Garmy1, Xiao-Jun Guo, Nadira Taïeb
1Laboratoire de Biochimie et Physicochimie des Membranes Biologiques, Faculté des Sciences de St-Jérôme, Université Paul Cézanne, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France.
Abstract:
The cellular isoform of the normal prion protein PrP(c), encoded by the PRNP gene, is expressed in human intestinal epithelial cells where it may represent a potential target for infectious prions. We have sequenced the PRNP gene in Caco-2 and HT-29 parental and clonal cell lines, and found that these cells have a distinct polymorphism at codon 129. HT-29 cells are homozygous Met/Met, whereas Caco-2 cells are heterozygous Met/Val. The 129Val variant was also detected in Caco-2 mRNAs. Real-time PCR quantifications revealed that PrP(c) mRNAs were more expressed in HT-29 cells than in Caco-2 cells. These data were confirmed by studying the expression of PrP(c) in plasma membranes and lipid rafts prepared from these cells. Overall, these results may be important in view of using human intestinal cell lines Caco-2 and HT-29 as cellular in vitro models to study the initial steps of prion propagation after oral inoculation.
Insights
Human intestinal cells Caco-2 and HT-29 express the prion protein PrP(c), a potential target for infectious prions. Genetic variations and expression levels were analyzed, offering insights into prion disease models.
Area of Science:
- Gastroenterology
- Neuroscience
- Molecular Biology
Background:
- The cellular prion protein (PrP(c)) is expressed in human intestinal epithelial cells.
- PrP(c) may serve as a target for infectious prions entering the body through the gut.
- Understanding PrP(c) expression and genetic variations in intestinal cells is crucial for prion disease research.
Purpose of the Study:
- To investigate the PRNP gene sequence and PrP(c) expression in Caco-2 and HT-29 intestinal cell lines.
- To identify and characterize prion protein polymorphisms in these cell lines.
- To evaluate the suitability of Caco-2 and HT-29 cells as in vitro models for studying prion propagation.
Main Methods:
- Sequencing of the PRNP gene in Caco-2 and HT-29 cell lines.
- Analysis of PRNP gene polymorphism at codon 129.
- Real-time PCR to quantify PrP(c) mRNA levels.
- Western blot analysis of PrP(c) expression in plasma membranes and lipid rafts.
Main Results:
- Caco-2 cells are heterozygous (Met/Val) at codon 129, while HT-29 cells are homozygous (Met/Met).
- The 129Val variant was detected in Caco-2 cell messenger RNAs (mRNAs).
- HT-29 cells exhibited higher PrP(c) mRNA expression compared to Caco-2 cells.
- PrP(c) expression levels in plasma membranes and lipid rafts corroborated mRNA findings.
Conclusions:
- Caco-2 and HT-29 cell lines possess distinct PRNP gene polymorphisms and differential PrP(c) expression levels.
- These human intestinal cell lines represent valuable in vitro models for investigating the initial stages of prion disease following oral exposure.
- The identified genetic variations and expression patterns provide a foundation for future prion research using these cellular models.
