Cited by 497Alzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis ResearchDementia and Cognitive Impairment Research

The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.

Tau Filament Formation in Transgenic Mice Expressing P301L Tau

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Götz, Jürgen, Chen, Feng, Barmettler, Robi, Nitsch, Roger M.·2001·Journal of Biological Chemistry

Abstract

Mutations in the microtubule-associated protein tau, including P301L, are genetically coupled to hereditary frontotemporal dementia with parkinsonism linked to chromosome 17. To determine whether P301L is associated with fibril formation in mice, we expressed the longest human tau isoform, human tau40, with this mutation in transgenic mice by using the neuron-specific mouse Thy1.2 promoter. We obtained mice with high expression of human P301L tau in cortical and hippocampal neurons. Accumulated tau was hyperphosphorylated and translocated from axonal to somatodendritic compartments and was accompanied by astrocytosis and neuronal apoptosis indicated by terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end-labeling staining. Moreover, P301L tau formed abnormal filaments. Electron microscopy of sarcosyl-insoluble protein extracts established that the filaments had a straight or twisted structure of variable length and were approximately 15 nm wide. Immunoelcecton microscopy showed that the tau filaments were phosphorylated at the TG3, AT100, AT8, and AD199 epitopes in vivo. In cortex, brain stem, and spinal cord, neurofibrillary tangles were also identified by thioflavin-S fluorescent microscopy and Gallyas silver stains. Together, our results show that expression of the P301L mutation in mice causes neuronal lesions that are similar to those seen in human tauopathies.

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Crossref · 10.1074/jbc.m006531200

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  1. Gallyas, 1971, Acta Morphol. Acad. Sci. Hung., 19, 1

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Metadata

Authors
Götz, J., Chen, F., Barmettler, R., & Nitsch, R. M.
Affiliations
University of Zurich (CH)
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-01
Volume
276
Issue
1
Pages
529-534
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2035156043
Cited by
495
References
26
Citations by year
2026: 5 · 2025: 9 · 2024: 29 · 2023: 13 · 2022: 20 · 2021: 18 · 2020: 16 · 2019: 17 · 2018: 9 · 2017: 16 · 2016: 10 · 2015: 11 · 2014: 15 · 2013: 22 · 2012: 18
FWCI
18.73
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
transgenic mice, tau hyperphosphorylation, neurofibrillary tangles, tauopathy, neuronal apoptosis, astrocyte activation
MeSH terms
Animals, Brain, Gliosis, Humans, Immunohistochemistry, Mice, Transgenic, Actin Cytoskeleton, Microscopy, Electron, Microscopy, Fluorescence, Mutation, Organ Specificity, Phosphorylation, Protein Conformation, Immunoblotting, Gene Expression, Neurofibrillary Tangles, tau Proteins, Apoptosis, Amino Acid Substitution, Protein Isoforms, In Situ Nick-End Labeling, Mice

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