ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2020
Developmental Pathogenicity of 4-Repeat Human Tau Is Lost with the P301L Mutation in Genetically Matched Tau-Transgenic Mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- A murine model of amyloid-enhanced tauopathy: Comparison of wild-type and P301L-tau.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Substrate Profiling of RNF216 Uncovers a Translation-Linked OTUD4 Regulatory Axis.bioRxiv : the preprint server for biology · 2026Article
- Non-mutated human tau stimulates Alzheimer's disease-relevant neurodegeneration in a microglia-dependent manner.Scientific reports · 2025Article
- Geometry based prediction of tau protein sites and motifs associated with misfolding and aggregation.Scientific reports · 2025Article
- Advancing Alzheimer's research by improving disease modeling of secondary tauopathy.NPJ dementia · 2025Review
- Mitochondrial Quality Control in Alzheimer's Disease: Insights fromAntioxidants (Basel, Switzerland) · 2024Review
- Brain Microvascular Pericyte Pathology Linking Alzheimer's Disease to Diabetes.Microcirculation (New York, N.Y. : 1994) · 2024Review
- DLK-MAPK Signaling Coupled with DNA Damage Promotes Intrinsic Neurotoxicity Associated with Non-Mutated Tau.Molecular neurobiology · 2024Article
- Pathological and physiological functional cross-talks of α-synuclein and tau in the central nervous system.Neural regeneration research · 2024Review
- Diagnostic and therapeutic targeting of pathological tau proteins in neurodegenerative disorders.FEBS open bio · 2024Review
- Deleterious and protective effects of epothilone-D alone and in the context of amyloid β- and tau-induced alterations.Frontiers in molecular neuroscience · 2023Article
- Limitations of human tau-expressing mouse models and novel approaches of mouse modeling for tauopathy.Frontiers in neuroscience · 2023Review
- Blocking Site-Specific Cleavage of Human Tau Delays Progression of Disease-Related Phenotypes in Genetically Matched Tau-Transgenic Mice Modeling Frontotemporal Dementia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons.Molecular brain · 2021Article
- Modified heptapeptide from tau binds both tubulin and microtubules.Thoracic cancer · 2020Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Tau is a microtubule-associated protein that becomes dysregulated in a group of neurodegenerative diseases called tauopathies. Differential tau isoforms, expression levels, promoters, and disruption of endogenous genes in transgenic mouse models of tauopathy make it difficult to draw definitive conclusions about the biological role of tau in these models. We addressed this shortcoming by characterizing the molecular and cognitive phenotypes associated with the pathogenic P301L tau mutation (rT2 mice) in relation to a genetically matched transgenic mouse overexpressing nonmutant (NM) 4-repeat (4R) human tau (rT1 mice). Both male and female mice were included in this study. Unexpectedly, we found that 4R NM human tau (hTau) exhibited abnormal dynamics in young mice that were lost with the P301L mutation, including elevated protein stability and hyperphosphorylation, which were associated with cognitive impairment in 5-month-old rT1 mice. Hyperphosphorylation of NM hTau was observed as early as 4 weeks of age, and transgene suppression for the first 4 or 12 weeks of life prevented abnormal molecular and cognitive phenotypes in rT1, demonstrating that NM hTau pathogenicity is specific to postnatal development. We also show that NM hTau exhibits stronger binding to microtubules than P301L hTau, and is associated with mitochondrial abnormalities. Overall, our genetically matched mice have revealed that 4R NM hTau overexpression is pathogenic in a manner distinct from classical aging-related tauopathy, underlining the importance of assaying the effects of transgenic disease-related proteins at appropriate stages in life.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.