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Enhanced levels of scrapie responsive gene mRNA in BSE-infected mouse brain
F Dandoy-Dron1, L Benboudjema, F Guillo
1Laboratoire d'Oncologie Virale, CNRS UPR 9045, 7 rue guy Moquet, BP8, IFC1, 94801, Villejuif cedex, France.
Abstract:
The expression of the mRNA of nine scrapie responsive genes was analyzed in the brains of FVB/N mice infected with bovine spongiform encephalopathy (BSE). The RNA transcripts of eight genes were overexpressed to a comparable extent in both BSE-infected and scrapie-infected mice, indicating a common series of pathogenic events in the two transmissible spongiform encephalopathies (TSEs). In contrast, the serine proteinase inhibitor spi 2, an analogue of the human alpha-1 antichymotrypsin gene, was overexpressed to a greater extent in the brains of scrapie-infected animals than in animals infected with BSE, reflecting either an agent specific or a mouse strain specific response. The levels of spi 2 mRNA were increased during the course of scrapie prior to the onset of clinical signs of the disease and the increase reached 11 to 45 fold relative to uninfected controls in terminally ill mice. Spi 2, in common with four of the other scrapie responsive genes studied, is known to be associated with pro-inflammatory processes. These observations underline the importance of cell reactivity in TSE. In addition, scrg2 mRNA the level of which is enhanced in TSE-infected mouse brain, was identified as a previously unrecognized long transcript of the murine aldolase C gene. However, the level of the principal aldolase C mRNA is unaffected in TSE. The increased representation of the longer transcript in the late stage of the disease may reflect changes in mRNA processing and/or stability in reactive astrocytes or in damaged Purkinje cells.
Insights
Researchers analyzed gene expression in mice with bovine spongiform encephalopathy (BSE) and scrapie. Eight genes showed similar overexpression, suggesting common disease pathways, while Spi 2 gene expression differed, highlighting agent-specific responses in transmissible spongiform encephalopathies (TSEs).
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Transmissible spongiform encephalopathies (TSEs) like scrapie and bovine spongiform encephalopathy (BSE) are neurodegenerative diseases.
- Understanding the molecular mechanisms and host responses in TSEs is crucial for developing diagnostic and therapeutic strategies.
- Gene expression analysis provides insights into cellular responses during disease progression.
Purpose of the Study:
- To compare the mRNA expression profiles of nine scrapie-responsive genes in FVB/N mice infected with BSE versus scrapie.
- To investigate the role of specific genes, such as serine proteinase inhibitor spi 2, in differential responses to different TSE agents.
- To identify novel transcripts associated with TSEs and understand their potential role in disease pathogenesis.
Main Methods:
- Quantitative analysis of mRNA expression levels for nine scrapie-responsive genes in the brains of BSE-infected and scrapie-infected FVB/N mice.
- Comparison of gene expression patterns between BSE-infected, scrapie-infected, and uninfected control mice.
- Identification and characterization of novel transcripts using techniques like Northern blotting or similar molecular assays.
Main Results:
- Eight out of nine analyzed genes showed comparable overexpression in both BSE- and scrapie-infected mice, suggesting conserved pathogenic pathways in TSEs.
- The serine proteinase inhibitor spi 2 mRNA was significantly more overexpressed in scrapie-infected mice compared to BSE-infected mice.
- A previously unrecognized long transcript of the murine aldolase C gene (scrg2 mRNA) was identified and found to be enhanced in TSE-infected brains, while the principal aldolase C mRNA remained unaffected.
Conclusions:
- The differential expression of Spi 2 suggests agent-specific or host-specific responses in TSEs.
- The observed increase in Spi 2 mRNA levels prior to clinical signs in scrapie indicates its potential as an early biomarker.
- The identification of scrg2 mRNA suggests altered mRNA processing or stability in reactive astrocytes or damaged Purkinje cells during TSEs, highlighting the importance of cellular reactivity.