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Mice devoid of the glial fibrillary acidic protein develop normally and are susceptible to scrapie prions
Open accessAbstract
Glial fibrillary acidic protein (GFAP) is an intermediate filament protein specifically expressed in astrocytes in the CNS. To examine the function of GFAP in vivo, the Gfap gene was disrupted by gene targeting in embryonic stem cells. Mice homozygous for the mutation were completely devoid of GFAP but exhibited normal development and showed no obvious anatomical abnormalities in the CNS. When inoculated with infectious scrapie prions, the mutant mice exhibited neuropathological changes typical of prion diseases. Infectious prions accumulated in brains of the mutant mice to a degree similar to that in control littermates. These results suggest that GFAP is not essential for the morphogenesis of the CNS or for astrocytic responses against neuronal injury. The results argue against the hypothesis that GFAP plays a crucial role in the pathogenesis of prion diseases.
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“Absence of GFAP and/or Vim in mice has no major effect under physiological conditions (17–20), reflecting the role of intermediate filament (nanofilament) system as a signaling platform in situations connected with cellular stress (21).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [18]
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Metadata
- Authors
- Gomi, H., Yokoyama, T., Fujimoto, K., Ikeda, T., Katoh, A., Itoh, T., & Itohara, S.
- Affiliations
- Kyoto University (JP)
- National Institute of Animal Health (JP)
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1995-01
- Volume
- 14
- Issue
- 1
- Pages
- 29-41
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2059028264
- Cited by
- 256
- References
- 67
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 1 · 2017: 8 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 6 · 2012: 6
- FWCI
- 7.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Science and Technology Agency
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- glial fibrillary acidic protein, prion disease, astrocytes, intermediate filaments, gene targeting, central nervous system development, prion accumulation, neuropathology, prion pathogenesis
- MeSH terms
- Animals, Astrocytes, beta-Galactosidase, Brain, Brain Chemistry, Female, Glial Fibrillary Acidic Protein, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Prions, RNA, Messenger, Scrapie, Spinal Cord, Vimentin, Mutagenesis, Gene Targeting, Mice
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