Tau filament formation in transgenic mice expressing P301L tau

Goetz, Juergen, Chen, Feng, Barmettler, Robi and Nitsch, Roger M. (2001) Tau filament formation in transgenic mice expressing P301L tau. Journal of Biological Chemistry, 276 1: 529-534. doi:10.1074/jbc.M006531200

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Author Goetz, Juergen
Chen, Feng
Barmettler, Robi
Nitsch, Roger M.
Title Tau filament formation in transgenic mice expressing P301L tau
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
1083-351X
Publication date 2001-01
Sub-type Article (original research)
DOI 10.1074/jbc.M006531200
Open Access Status File (Publisher version)
Volume 276
Issue 1
Start page 529
End page 534
Total pages 6
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Formatted 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 ~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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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