Research Models

TPM (Thy-1 PS1.M146V)

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Species: Mouse
Genes: PSEN1
Mutations: PSEN1 M146V
Modification: PSEN1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: Transgene injected into fertilized oocytes from pure C57BL/6 mice.
Availability: Unknown

Summary

This transgenic mouse model was generated by scientists at GlaxoSmithKline. Reports describing the phenotypic characterization of this mouse as a single transgenic are sparse in the published literature. It is best known for being one of the parental strains used to generate the TASTPM double transgenic, which develops amyloid pathology and cognitive deficits (Howlett et al., 2004).

Modification Details

Transgene encoding human PSEN1 carrying the M146V mutation. Transgene is driven by the murine Thy-1 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 TPM mice, users of this model should be aware of the findings in 5xFAD mice when designing and documenting breeding strategies.

Related Strains

TASTPM: A double transgenic generated by crossing the TPM model with another trangenic line, TAS10, which expresses mutant human APP.

Last Updated: 31 Jan 2025

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References

Research Models Citations

  1. 5xFAD (C57BL6)
  2. TASTPM (TAS10 x TPM)
  3. TAS10 (thy1-APPswe)

Paper Citations

  1. Howlett DR, Richardson JC, Austin A, Parsons AA, Bate ST, Davies DC, Gonzalez MI. Cognitive correlates of Abeta deposition in male and female mice bearing amyloid precursor protein and presenilin-1 mutant transgenes. Brain Res. 2004 Aug 13;1017(1-2):130-6. PubMed.
  2. 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.

Further Reading