Research Models

TMHT (Thy-1 mutated human tau)

Synonyms: TAU 441, hTAU441, TAU441 V337M R406W

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Species: Mouse
Genes: MAPT
Mutations: MAPT V337M, MAPT R406W
Modification: MAPT: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: C57Bl/6xDBA
Availability: The CRO Scantox Neuro offers research services with this line.

Neuropathology

Increased total tau and phosphorylated tau species (Thr181, Ser199, Thr231) in the amygdala and hippocampus starting at three months.

Cognition/Behavior

Spatial memory deficits starting at five months by the Morris water maze. Olfactory deficits at five months indicated by the buried food test. No motor deficits (by rotarod, beam walk) or depressive behavior as indicated by the forced swim test.

Modification Details

Transgene consists of human MAPT Tau441 (2N/4R) with mutations V337M and R406W under control of the Thy1 promoter.

The parental origin of the transgenes was shown to influence AD-related pathology in another model, 5xFAD (C57BL6), in which the Thy1 promoter drives transgene expression, possibly due to genomic imprinting of the promoter (Sasmita et al., 2025). While this phenomenon has not yet been demonstrated in TMHT mice, users of this model should be aware of the findings in 5xFAD mice when designing and documenting breeding strategies.

Availability

The contract research organization Scantox Neuro offers research services with this line.

Phenotype Characterization

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

Absent

  • Plaques

No Data

Plaques

Absent.

Tangles

Tangles at 4 months and progress with age.

Cognitive Impairment

Cognitive impairment by 5 months as measured by the Morris Water Maze.

Last Updated: 31 Jan 2025

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References

Research Models Citations

  1. 5xFAD (C57BL6)

Paper Citations

  1. Sasmita AO, Ong EC, Nazarenko T, Mao S, Komarek L, Thalmann M, Hantakova V, Spieth L, Berghoff SA, Barr HJ, Hingerl M, Börensen F, Hirrlinger J, Simons M, Stevens B, Depp C, Nave KA. Parental origin of transgene modulates amyloid-β plaque burden in the 5xFAD mouse model of Alzheimer's disease. Neuron. 2025 Jan 20; Epub 2025 Jan 20 PubMed.

External Citations

  1. Scantox Neuro
  2. Scantox Neuro

Further Reading

No Available Further Reading