Research Models

TAU R406W

Synonyms: TgTauR406W

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Species: Mouse
Genes: MAPT
Mutations: MAPT R406W
Modification: MAPT: Transgenic
Disease Relevance: Frontotemporal Dementia, Alzheimer's Disease
Strain Name: N/A
Genetic Background: B6SJL/F1; backcrossed to C57BL/6J
Availability: Unknown.

Modification Details

Transgene containing human 4-repeat tau cDNA with the R406W mutation containing myc and FLAG tags at N-and C-terminal ends, respectively, and driven by the CaMK-II promoter.

Neuropathology

Argyrophilic and congophilic tau inclusions in neurons of the forebrain with age, 18 months of age. Detectable with Congo red, thioflavin S and Gallyas silver stain. Congophilic tau inclusions also in the hippocampus and amygdala. Mainly straight tau filaments (Tatebayashi et al., 2002).

Cognition/Behavior

Impairments in the contextual and cued fear conditioning test at 16–23 months compared with wild-type littermates. No detectable sensorimotor deficits.

Other Phenotypes

No differences from wild-type in body weight, sensorimotor reflexes (acoustic startle response), or motor coordination (accelerating rotarod and pole tests).  Attenuation of the Schaffer collateral-evoked neural response in hippocampal slices. Decrease in prepulse inhibition. Higher mortality.

Phenotype Timeline

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Observed

Absent

  • Plaques

Unknown

  • Neuronal Loss
  • Gliosis
  • Synaptic Loss
  • Changes in LTP/LTD

Plaques

Absent.

Tangles

Congophilic tau inclusions in a subset of forebrain neurons around 18 months of age. Detected by Congo red, thioflavin S, and Gallyas silver stain.

Neuronal Loss

Unknown.

Gliosis

Unknown.

Synaptic Loss

Unknown.

Changes in LTP/LTD

Unknown.

Cognitive Impairment

Impairments in the contextual and cued fear conditioning test at 16–23 months compared with wild-type littermates. No detectable sensorimotor deficits.

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References

Paper Citations

  1. . Tau filament formation and associative memory deficit in aged mice expressing mutant (R406W) human tau. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13896-901. PubMed.

Further Reading

No Available Further Reading