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Scrapie in mice deficient in apolipoprotein E or glial fibrillary acidic protein
1Department of Neurology, University of California, San Francisco 94143-0518, USA.
Abstract:
In the prion diseases, extensive reactive gliosis is often found to be out of proportion to the degree of apparent neuronal damage. To evaluate the role of astrocytic gliosis in experimental scrapie of the mouse, we inoculated mice deficient in apolipoprotein E (apoE) or the glial fibrillary acidic protein (GFAP) with mouse prions. The expression of both apoE and GFAP in astrocytes increases as part of the reactive gliosis that accompanies scrapie. Null mice deficient in either apoE or GFAP inoculated with prions exhibited incubation times indistinguishable from untargeted control mice. The level of PrPSc and its regional deposition in the brains of ill mice deficient in either protein were also similar to control mice. Our findings demonstrate that neither apoE nor GFAP participates in the pathogenesis of the disease or in the production of PrPSc.
Insights
This study investigated reactive gliosis in prion diseases. Findings show that apolipoprotein E (apoE) and glial fibrillary acidic protein (GFAP) do not influence prion disease progression or PrPSc production.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Prion diseases are characterized by reactive gliosis, an increase in glial cells, often disproportionate to neuronal damage.
- Apolipoprotein E (apoE) and glial fibrillary acidic protein (GFAP) are upregulated in astrocytes during reactive gliosis in scrapie.
Purpose of the Study:
- To investigate the role of astrocytic gliosis, specifically apoE and GFAP, in the pathogenesis of experimental scrapie in mice.
- To determine if the absence of apoE or GFAP affects prion disease incubation times or PrPSc accumulation.
Main Methods:
- Mice genetically modified to be deficient in either apolipoprotein E (apoE) or glial fibrillary acidic protein (GFAP) were inoculated with mouse prions.
- Incubation times, clinical signs, and prion protein scrapie (PrPSc) levels and distribution in the brain were compared between knockout mice and control mice.
Main Results:
- Mice deficient in apoE or GFAP exhibited incubation times for scrapie that were indistinguishable from those of control mice.
- The levels and regional deposition of PrPSc in the brains of ill mice lacking apoE or GFAP were similar to those in control mice.
Conclusions:
- Neither apolipoprotein E (apoE) nor glial fibrillary acidic protein (GFAP) plays a significant role in the pathogenesis of experimental prion disease (scrapie).
- These proteins are not essential for the production or propagation of the disease-associated prion protein, PrPSc.