Species: Mouse
Genes: APP
Mutations: APP K670_M671delinsNL (Swedish)
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: Transgene injected into C57BL/6 x C3H oocytes, some backcrossing to C57BL/6
Availability: Unknown

Summary

This transgenic mouse overexpresses human APP carrying the Swedish mutation. The mouse develops age-related amyloid pathology and cognitive deficits. It does not develop tangle pathology or appreciable neuronal loss (Richardson et al., 2003).

In this model, the APP transgene is under the control of the Thy-1 promoter, driving robust expression in the forebrain. The mice accumulate Aβ40 and Aβ42 in the cortex and hippocampus, with higher overall levels in the cortex. Amyloid pathology develops by 12 months of age in both brain regions. Plaque pathology, including mature fibrillar plaques, increases progressively up to 24 months of age. Starting around six months of age, and prior to extensive plaque deposition, astrogliosis and microgliosis begin in the dentate gyrus and dystrophic neurites are observed. Ultrastructural changes in synaptic morphology, including active zone area and synaptic density, suggest that TAS10 mice have smaller but more numerous synapses than non-Tg mice at 12 and 18 months of age. However, the number of synapses then drops off sharply in TAS10 mice, leaving them with fewer synapses than non-Tg mice by 24 months of age. Deficits in basal synaptic transmission have been observed in the CA1 region of the hippocampus at 12 to 14 months, but short-term and long-term synaptic plasticity appear normal even at an age when neuropathological changes are well underway (Brown et al., 2005). TAS10 mice have an elevated number of lysosomes from an early age, starting around six months, as shown by electron microscopy (Richardson et al., 2003).

TAS10 mice show deficits in spatial memory prior to Aβ deposition. Deficits in the Morris water maze are observed as early as six months of age. Deficits in spontaneous alternation behavior in the Y maze occur later, around 12 months of age. No deficit in fear conditioning has been observed, up to 24 months of age (Richardson et al., 2003).

Modification Details

These mice express a transgene encoding human APP (isoform 695) harboring the Swedish mutation. The 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 TAS10 (thy1-APPswe) 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 TAS10 model with another trangenic line, TPM, which expresses mutant human PSEN1.

Phenotype Characterization

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References

Research Models Citations

1. 5xFAD (C57BL6)
2. TASTPM (TAS10 x TPM)
3. TPM (Thy-1 PS1.M146V)

Paper Citations

1. Richardson JC, Kendal CE, Anderson R, Priest F, Gower E, Soden P, Gray R, Topps S, Howlett DR, Lavender D, Clarke NJ, Barnes JC, Haworth R, Stewart MG, Rupniak HT. Ultrastructural and behavioural changes precede amyloid deposition in a transgenic model of Alzheimer's disease. Neuroscience. 2003;122(1):213-28. PubMed.
2. Brown JT, Richardson JC, Collingridge GL, Randall AD, Davies CH. Synaptic transmission and synchronous activity is disrupted in hippocampal slices taken from aged TAS10 mice. Hippocampus. 2005;15(1):110-7. PubMed.
3. 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