Overview

Also Known As: 3xTg-AD congenic 129S4 mice

These 3xTg-AD mice harbor a Psen1 mutation (M146V) and the co-injected APPSwe and tauP301L transgenes (Tg(APPSwe,tauP301L)1Lfa)), and may be useful for studying plaque and tangle pathology associated with synaptic dysfunction and Alzheimer's disease.

Donating Investigator

Frank LaFerla, University of California, Irvine

Genetic overview

Genetic Background	Generation

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Research Applications

Neurobiology Research
Developmental Biology Research
Research Tools
Mouse/Human Gene Homologs

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Base Price

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Details

Detailed Description

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described for 3xTg‐AD mice on a C57BL/6;129 genetic background (see Stock No. 004807). We will modify the strain description if necessary as published results become available. Unless noted otherwise, the information below describes C57BL/6;129 genetic background 3xTg‐AD mice.

Mice homozygous for all three mutant alleles (3xTg-AD; homozygous for the Psen1 mutation and homozygous for the co-injected APPSwe and tauP301L transgenes (Tg(APPSwe,tauP301L)1Lfa)) are viable, fertile and display no initial gross physical or behavioral abnormalities. Translation of the overexpressed transgenes appears to be restricted to the central nervous system, notably in Alzheimer's disease-relevant areas including the hippocampus and cerebral cortex. The initial characterization of this mouse line indicated a progressive increase in amyloid beta peptide deposition, with intracellular immunoreactivity being detected in some brain regions as early as 3-4 months. Synaptic transmission and long-term potentiation are demonstrably impaired in mice 6 months of age. Between 12-15 months aggregates of conformationally altered and hyperphosphorylated tau are detected in the hippocampus. This mutant mouse exhibits plaque and tangle pathology associated with synaptic dysfunction, traits similar to those observed in Alzheimer's disease patients.

In February 2014, the donating investigator communicated that, in contrast to the initial observations, male transgenic mice may not exhibit the phenotypic traits originally described. No reports of diminished traits in female carriers have been reported.

Belfiore et al. 2019 Aging Cell 18:e12873 [PMID:30488653] characterized C57BL/6;129 genetic background 3xTg‐AD females for the onset, severity, and incidence of amyloidβ, phosphorylated tau, hippocampal and cortical plaques, neuroinflammation and cognitive decline. Most phenotypes that were evaluated were evident by 6 months of age. However, it was noted that cortical plaques were first detected at 12 months. For more detailed information, please see that publication. If any more detailed characterization is completed by The Jackson Laboratory, we will modify the strain description accordingly.

Development

Single-cell embryos from mice bearing the presenilin PS1M146V knock-in mutation on a mixed C57BL/6;129X1/SvJ;129S1/Sv genetic background (B6;129-Psen1^tm1Mpm) were co-injected with two independent mutant human transgenes; amyloid beta precursor protein (APPSwe) and microtubule-associated protein tau (tauP30IL). Both transgenes integrated at the same locus and are under the control of the mouse Thy1.2 regulatory element. Founder mice (line B1) were mated to B6;129-Psen1^tm1Mpm mice. Offspring from this cross were bred together, resulting in mice homozygous for all three alleles (3xTg-AD; homozygous for the Psen1 mutation and homozygous for the co-injected APPSwe and tauP301L transgenes, Tg(APPSwe,tauP301L)1Lfa). The mice were then backcrossed to 129/SvJaeSorMgr for 11 generations before being inter-crossed. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize 129S4/SvJaeJ oocytes (Stock No. 009104). The transgene inserted on Chromosome 2 causing a 3 bp deletion.

Control Suggestions

Approximate Controls

009104 129S4/SvJaeJ

Additional Information

Considerations for Choosing Controls

Genetics

Currently there are no related genes or alleles for this strain.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Neurobiology Research
- Neurodevelopmental Defects
- Alzheimer's Disease
  - APP mutants
  - Tau (Mapt) mutants
  - APP and PSEN1 mutants
  - Presenilin mutants
  - strains expressing mutant APP
- Behavioral and Learning Defects
- Neurodegeneration
Developmental Biology Research
- Postnatal Lethality
  - Homozygous
- Skeletal Defects
- Neurodevelopmental Defects
Research Tools
- Neurobiology Research
Mouse/Human Gene Homologs
- Alzheimer's

Mammalian Phenotype Terms by Genotype

References

Technical Support

Contact Technical Support

Genotyping Protocols
- End Point Analysis:Psen1^tm1Mpm-EP
- QPCR:Tg(APPSwe,tauP301L)1Lfa
- Standard PCR:Tg(TAU*P301S)#Elan
- Probe:Tg(APPSwe,tauP301L)1Lfa
- Probe:Tg(APPSwe,tauP301L)1Lfa-Chr2
- QPCR:GQC-Cntn6 qPCR
- QPCR:GQC-Chl1 qPCR
- QPCR:GQC-Cntn3 qPCR
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live congenic colony, mice that are homozygous for the co-injected APPSwe and tauP301L transgenes [Tg(APPSwe,tauP301L)1Lfa on chromosome 2] and homozygous for the PS1M146V knock-in mutation [Psen1^tm1Mpm on chromosome 12] may be bred together.
- Additional Breeding and Husbandry Support
Mating System
- HOM HOM X HOM HOM
Citation
When using the 3xTg-AD congenic 129S4 mice mouse strain in a publication, please cite the originating article(s) and include JAX stock #031988 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Not-For-Profit & Academic Pricing

Service	Genotype	Price
	Hemizygous forTg(APPSwe,tauP301L)1Lfa and Heterozygous for Psen1<tm1Mpm>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Questions about Terms of Use

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Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

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Also Known As: 3xTg-AD congenic 129S4 mice

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

References

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Not-For-Profit & Academic Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability