Species: Mouse
Genes: MAPT
Mutations: MAPT R406W
Modification: MAPT: Transgenic
Disease Relevance: Frontotemporal Dementia
Strain Name: N/A
Genetic Background: C57BL6 x C3H, maintained in B6C3 background
Availability: Unknown

Neuropathology

Age-dependent increase in tau. Neurofibrillary-tangle-like pathology (filamentous intraneuronal tau aggregates), especially in the hippocampus. Neurodegeneration. Extensive gliosis in the brain and spinal cord.

Cognition/Behavior

Progressive motor weakness with advancing age, as demonstrated by dystonic movements of the hindlimbs when lifted by the tail.

Other Phentoypes

Altered microtubule binding and slow axonal transport of tau. Reduced lifespan.

Modification Details

Longest form of human tau carrying the R406W mutation driven by the mouse prion promoter.

Note

Three lines of R406W transgenic mice were generated (lines 37, 60, and 65). The best-characterized line, line 37, had human tau levels approximately 8- to 10-fold higher than endogenous murine tau (Zhang et al., 2004).

COMMENTS / QUESTIONS

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References

Paper Citations

1. Zhang B, Higuchi M, Yoshiyama Y, Ishihara T, Forman MS, Martinez D, Joyce S, Trojanowski JQ, Lee VM. Retarded axonal transport of R406W mutant tau in transgenic mice with a neurodegenerative tauopathy. J Neurosci. 2004 May 12;24(19):4657-67. PubMed.

Further Reading

No Available Further Reading