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Developmental influence of the cellular prion protein on the gene expression profile in mouse hippocampus
- Source :
- Physiological Genomics. 43:711-725
- Publication Year :
- 2011
- Publisher :
- American Physiological Society, 2011.
-
Abstract
- The conversion of the cellular prion protein (PrPC) to an abnormal and protease-resistant isoform is the key event in prion diseases. Mice lacking PrPCare resistant to prion infection, and downregulation of PrPCduring prion infection prevents neuronal loss and the progression to clinical disease. These results are suggestive of the potential beneficial effect of silencing PrPCduring prion diseases. However, the silencing of a protein that is widely expressed throughout the central nervous system could be detrimental to brain homeostasis. The physiological role of PrPCremains still unclear, but several putative functions (e.g., neuronal development and maintenance) have been proposed. To assess the influence of PrPCon gene expression profile in the mouse brain, we undertook a microarray analysis by using RNA isolated from the hippocampus at two different developmental stages: newborn (4.5-day-old) and adult (3-mo-old) mice, both from wild-type and Prnp0/0animals. Comparing the different datasets allowed us to identify “commonly” co-regulated genes and “uniquely” deregulated genes during postnatal development. The absence of PrPCaffected several biological pathways, the most representative being cell signaling, cell-cell communication and transduction processes, calcium homeostasis, nervous system development, synaptic transmission, and cell adhesion. However, there was only a moderate alteration of the gene expression profile in our animal models. PrPCdeficiency did not lead to a dramatic alteration of gene expression profile and produced moderately altered gene expression levels from young to adult animals. Thus, our results may provide additional support to silencing endogenous PrPClevels as therapeutic approach to prion diseases.
- Subjects :
- Gene isoform
Mouse Hippocampus
Prions
Reverse Transcriptase Polymerase Chain Reaction
Physiology
Gene Expression Profiling
animal diseases
Blotting, Western
Age Factors
Genetic Therapy
Biology
Microarray Analysis
Hippocampus
Molecular biology
Prion Proteins
Prion Diseases
nervous system diseases
Mice
Prion infection
Gene Expression Regulation
Gene expression
Genetics
Animals
Gene Silencing
Prion protein
Subjects
Details
- ISSN :
- 15312267 and 10948341
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- Physiological Genomics
- Accession number :
- edsair.doi.dedup.....691990a338876e44692ad76f0ad50a77