What question did this study set out to answer?

To develop a physiologically relevant mouse model expressing all human tau isoforms to investigate pathological tau propagation and its interaction with beta-amyloid pathology.

July 5, 2019Journal of Biological ChemistryOpen Access

Humanization of the entire murine Mapt gene provides a murine model of pathological human tau propagation

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Authors

TSTakashi SaitoNagoya City University NMNaomi MihiraRIKEN Center for Brain Science YMYukio MatsubaShiga University of Medical Science

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Implication

Genetic knock-in study demonstrates accelerated pathological tau propagation in humanized Mapt mice, indicating species-specific transmission dynamics in Alzheimer's disease.

Key Points

To develop a physiologically relevant mouse model expressing all human tau isoforms to investigate pathological tau propagation and its interaction with beta-amyloid pathology.
Generated knock-in mice by replacing the entire murine Mapt gene with the human MAPT ortholog using homologous recombination.
Cross-bred humanized MAPT knock-in mice with single App knock-in mice to establish a double-knock-in model of Alzheimer's disease etiology.
Inoculated mice with Alzheimer's disease brain-derived pathological tau to evaluate cell-to-cell propagation dynamics in the presence and absence of Aβ-amyloidosis.
Humanized MAPT knock-in mice successfully expressed all six human tau isoforms, with double-knock-in mice showing elevated tau phosphorylation compared to single MAPT knock-in controls.
Tau humanization significantly accelerated the cell-to-cell propagation of Alzheimer's disease-derived pathological tau across brain regions.
Co-occurring Aβ-amyloidosis intensified pathological tau accumulation around dystrophic neurites, driven by preferential binding between human tau molecules over murine tau.

Cite This Study

Saito et al. (2019) studied this question.

synapsesocial.com/papers/6a9880aa1ec081155cd317d8 https://doi.org/10.1074/jbc.ra119.009487

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Implication

Genetic knock-in study demonstrates accelerated pathological tau propagation in humanized Mapt mice, indicating species-specific transmission dynamics in Alzheimer's disease.

Humanization of the entire murine Mapt gene provides a murine model of pathological human tau propagation

Discussion

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Implication

Key Points

Cite This Study

Humanization of the entire murine Mapt gene provides a murine model of pathological human tau propagation

Discussion

Member takes

Implication

Key Points

Cite This Study

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