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APP/Ps1/Tau triple-transgenic mice

Jiangsu Aniphe BioLab has established a comprehensive management system for transgenic mouse resources. Leveraging standardized breeding, genotyping, and animal quality‑control protocols, it offers APP/PS1/Tau triple‑transgenic mouse models at various ages. These models exhibit stable phenotypes and consistent experimental batch performance, supporting research on Alzheimer’s disease mechanisms, target validation, and drug efficacy evaluation, thereby accelerating the development of therapies for neurodegenerative diseases.

Strain Introduction

The APP/Ps1/Tau triple-transgenic mouse (commonly referred to as the 3xTg-AD mouse) is one of the most effective animal models currently available for simultaneously replicating the two hallmark pathologies of Alzheimer’s disease (AD): β‑amyloid (Aβ) plaques and tau protein neurofibrillary tangles.

This model harbors three familial Alzheimer’s disease–associated mutations—APP Swedish (K670N/M671L), PS1 M146V, and tau P301L—and progressively recapitulates Aβ deposition, tau hyperphosphorylation, synaptic dysfunction, glial activation, and progressive cognitive decline within a single animal. It features a well-defined pathological timeline and pronounced sex differences, making it the most widely used multigene model in Alzheimer’s disease mechanistic studies and drug development.

Product Advantages

Recreating the dual-core pathology of AD

Aβ plaques and tau neurofibrillary tangles develop sequentially within the same mouse, faithfully recapitulating the hallmark pathological features of Alzheimer’s disease.

Age-dependent progressive disease course

Pathogenesis progresses in an orderly fashion: Aβ deposition precedes the onset of tau pathology, with lesions spreading from the cortex to the hippocampus, thereby facilitating staged interventions and the investigation of therapeutic windows.

Study on the Interaction Mechanism Between Aβ and Tau

It is suitable for validating the Aβ‑initiated tau pathology hypothesis and elucidating the molecular pathways through which the two synergistically mediate neuroinflammation and synaptic damage.

Covers multi-level degenerative lesions.

It exhibits both early synaptic plasticity impairment and cognitive decline, with neuronal loss observed in the elderly, thereby satisfying the requirements for a comprehensive pharmacological evaluation spanning from functional abnormalities to structural neural damage.

One-stop drug screening platform

This model enables the independent evaluation of Aβ‑targeting, tau‑targeting, or dual‑target combination therapies, thereby minimizing experimental errors introduced by switching among multiple models and enhancing translational relevance.

Data parameters

Strain Name

B6;129-Tg(APPSwe,tauP301L)1Lfa Psen1tm1Mpm/Mmj
Targeted gene

APP: transgenic; PSEN1: transgenic; MAPT: transgenic
Mutant site

APP KM670/671NL (Swedish), MAPT P301L, PSEN1 M146V
Genetic background

B6129SF2/J (i.e., the F2 generation derived from C57BL/6 and 129S mice)
Microbial Grade

SPF grade
Fur color

Black
Available by week of age

3 weeks of age and older

Validate data

The influence of genotype on phenotype

Homozygotes: The homozygous mice of the T3 transgenic line are viable and fertile. Cognitive deficits begin to emerge at 4 months of age. Amyloid‑β peptide deposition becomes detectable by 6 months (though it may be present as early as 3–4 months, it is not yet observable). Subsequently, neurofibrillary tangles appear in the hippocampus and cortex, and senile plaques can be observed in the frontal cortex. Between 12 and 15 months, aggregates of conformationally altered, hyperphosphorylated tau protein are detected in the hippocampus.

Heterozygote: The transgenic phenotype of a heterozygote is similar to that of a homozygote.

Heterozygote: The heterozygous knockout phenotype is similar to that of the wild type.

Note: A hemizygote refers to a male carrying a mutation on the X chromosome, or to a mouse of either sex that carries an inserted transgene without a homologous allele on the other chromosome.

Strain Establishment

Preliminary characterization of this mouse strain reveals a progressive accumulation of amyloid‑β deposits, with intracellular immunoreactivity detectable in certain brain regions as early as 3–4 months of age. By 6 months, synaptic transmission and long-term potentiation are significantly impaired. At 12–15 months, conformationally altered, hyperphosphorylated tau protein aggregates can be detected in the hippocampus. These mutant mice exhibit plaque and neurofibrillary tangle pathology associated with synaptic dysfunction—features that closely resemble those observed in Alzheimer’s disease patients.

 

Application areas

● Research on the pathogenesis of AD: At the same time, we will elucidate the interactions between Aβ and tau, their mechanisms of propagation, and the downstream signaling pathways.
● Preclinical pharmacological evaluation: Test candidate drugs—such as small molecules, antibodies, and gene therapies—that target Aβ, tau, or neuroinflammation, and evaluate their effects on dual pathology and cognitive function.
● Biomarker Development: Used for time‑dependent studies and mass spectrometric validation of biomarkers such as Aβ, p‑tau, and neurofilament light chain (NfL) in cerebrospinal fluid and plasma.
● Imaging studies: Small-animal PET/MRI tracers for Aβ and tau, or assessments of brain volume and white matter integrity.
● Neuroimmunology and Metabolism Research: Investigate the roles of glial–neuronal interactions and insulin signaling abnormalities in the progression of Alzheimer’s disease.
● Lifestyle intervention: Assess the effects of non-pharmacological interventions, such as diet, exercise, and environmental enrichment, on AD-like phenotypes.

Breeding Techniques and Precautions

Strictly control inbreeding systems to mitigate genetic divergence.

Environment and Caging Conditions

The housing environment is maintained at a constant temperature of 20–24°C and a relative humidity of 40–70%, with a 12-hour light–dark cycle under dim lighting. Strong light, noise, and high‑velocity air currents are avoided to prevent seizure induction. Sterilized bedding material (at least 2 cm thick) is used; for aged or frail rats, additional nesting material is provided to reduce stress. Bedding is partially replaced weekly, with the old bedding retained. Nesting shelters and chew blocks are placed inside the cages, while running wheels are prohibited, and enrichment items are regularly sterilized.

 

Strictly control environmental stimuli to reduce experimental stress.

Food and drink

Routine standard feed is sufficient; for 12-month-old aged rats, as well as for emaciated individuals and those with dental abnormalities, supplement with a paste‑like moist diet. Check the water supply daily and adjust the water bottle height to accommodate slower locomotion.

Provide filtered drinking water to rats to ensure clean water intake.

Literature support

References: Belfiore R; Rodin A; Ferreira E; Velazquez R; Branca C; Caccamo A; Oddo S. 2019. Temporal and regional progression of Alzheimer's disease-like pathology in 3xTg-AD mice. Aging Cell 18(1):e2873 PubMed: 30488653 MGI:J:273259
Scientific publications based on this model, as cited by Aniphe customers, are supported for submission to SCI-indexed journals. (Original paper link)
https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c01731

Frequently Asked Questions

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Q1: What are the phenotypic differences between female and male 3xTg-AD mice? What experimental considerations should be taken into account?

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A: In female mice, Aβ and tau pathology typically onset earlier and is more severe than in males, with more pronounced cognitive deficits—similar to the sex differences observed in human Alzheimer’s disease. Therefore:
● When testing preventive interventions, it is recommended to conduct sex‑stratified analyses, with at least 12 animals per sex group to ensure adequate statistical power.
● If only a single sex is selected, the rationale must be clearly stated (e.g., targeting estrogen‑related mechanisms) to avoid generalizing findings to all sexes.
● During behavioral testing, account for the influence of the female rats’ estrous cycle on locomotor activity; if necessary, assess the estrous stage via vaginal smears after testing to adjust for this confounding factor.

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Q2: When purchasing or breeding 3xTg-AD mice, how should the age at weaning be selected? What age range is recommended for different experimental purposes?

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● Preventive intervention studies: If the aim is to assess whether a drug can delay disease onset, it is recommended to initiate treatment at 3–4 months of age—when pathology has not yet fully manifested, with only intracellular Aβ and early synaptic alterations—and to continue until 9–12 months of age. This approach allows simultaneous evaluation of the drug’s preventive effects on Aβ deposition and early tau phosphorylation.
● Therapeutic intervention studies: If the goal is to reverse or mitigate established pathology, treatment may be initiated at 9–12 months of age—when Aβ plaques and tau hyperphosphorylation are already well established—and continued until 15–18 months of age, with assessments focused on improvements in late-stage neurofibrillary tangles and neuroinflammation.
● Cognitive phenotype screening: Significant deficits can typically be detected in hippocampus‑dependent tasks as early as 6–9 months of age, making this stage suitable for behavioral drug screening; moreover, animals at this age still exhibit robust motor abilities, thereby minimizing the confounding effects of age‑related motor impairments.
● Only Aβ/tau pathology sampling is required: Aβ plaques typically appear at 12 months of age, while tau tangles typically emerge between 15 and 18 months; the termination age can be selected based on whether a single or dual biomarker assessment is desired.
When making a purchase, confirm the precise age of the animals with the supplier and request a wild-type control from the same litter. If the experimental period is lengthy, order a sufficient number of animals in a single batch to minimize batch effects.

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