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

Tg(APPSwe,tauP301L)1Lfa

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

Psen1^tm1Mpm

Allele Type	Gene Symbol	Gene Name
Targeted	Psen1	presenilin 1

View Genetics

Research Applications

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

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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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.

Expression Data

Expressed Gene	APP, amyloid beta precursor protein, human
Expressed Gene	MAPT, microtubule associated protein tau, human
Site of Expression
Site of Expression

Control Suggestions

Approximate Controls

009104 129S4/SvJaeJ

Additional Information

Considerations for Choosing Controls

Selected References

Romberg C; Mattson MP; Mughal MR; Bussey TJ; Saksida LM. 2011. Impaired attention in the 3xTgAD mouse model of Alzheimer's disease: rescue by donepezil (Aricept). J Neurosci 31(9):3500-7PubMed: 21368062 MGI: J:170670

View All References

Genetics

Tg(APPSwe,tauP301L)1Lfa

Allele Symbol: Tg(APPSwe,tauP301L)1Lfa

Allele Name	transgene insertion 1, Frank M LaFerla
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	Tg(APPSwe,tauP301L)1Lfa; transgene insertion 1, Frank M LaFerla
Gene Symbol and Name	Tg(APPSwe,tauP301L)1Lfa, transgene insertion 1, Frank M LaFerla
Gene Synonym(s)
Promoter	Thy1, thymus cell antigen 1, theta, mouse, laboratory
Expressed Gene	APP, amyloid beta precursor protein, human
Expressed Gene	MAPT, microtubule associated protein tau, human
Strain of Origin	Not Specified
Chromosome	2
Molecular Note	To develop a model of Alzheimer's Disease, mice harboring mutant human APP (Swedish double mutation; K670N, M671L) and MAPT (P301L) as well as Psen^tm1Mpm were generated by microinjection of the APP and MAPT transgenic constructs into single cell embryos harvested from mice homozygous for Psen1^tm1Mpm. Southern blot analysis indicated that both transgenic constructs integrated into the same site. Western blot analysis showed APP and MAPT levels to be ~4 fold higher in hemizygous mice and ~6 (APP) to ~7 (Mapt) fold higher homozygous mice, relative to non transgenic mice. Amyloid-Beta peptide (both 40 and 42) was detected in transgenic mice, with greater levels in homozygous mice than in hemizygous mice. Expression was confined to the CNS. Highest steady state levels of proteins were detected in Alzheimer's Disease related regions including the hippocampus and cerebral cortex. Transgenic protein was not detected in the cerebellum. The transgene inserted on Chr 2 causing a 3 bp deletion.

Psen1^tm1Mpm

Allele Symbol: Psen1^tm1Mpm

Allele Name	targeted mutation 1, Mark P Mattson
Allele Type	Targeted
Allele Synonym(s)	targeted mutation 1, Mark P Mattson; Psen1^tm1Mpm
Gene Symbol and Name	Psen1, presenilin 1
Gene Synonym(s)	alzheimer disease 3 homolog; S182; Ad3h; AD3; Ad3h; presenilin-1; PS-1; PS1; FAD; ACNINV3
Promoter	Psen1, presenilin 1, mouse, laboratory
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	12
Molecular Note	Point mutations were introduced into the coding region of exon 5 that altered the codons corresponding to amino acids 145 and 146 from isoleucine and methionine to valine and valine, respectively, and a BstEII restriction site. A lox-P flanked neomycin cassette was also introduced into exon 4. F2 mice exhibited the expected polymorphism of the targeted allele when genomic DNA was amplified with exon 5 specific primers and the products were digested with the appropriate restriction enzyme. Northern blot analysis of total brain RNA using a Psen1 specific antibody showed that the targeted allele was expressed at normal physiological levels in homozygous mutant mice.
Mutations Made By	George Martin, University of Washington

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Alzheimer's disease

Research Areas By Phenotype

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

Genotype: Psen1^tm1Mpm related

Neurobiology Research
- Neurodegeneration
- Neurodevelopmental Defects
- Alzheimer's Disease
- Behavioral and Learning Defects
Mouse/Human Gene Homologs
- Alzheimer's
Developmental Biology Research
- Postnatal Lethality
  - Homozygous
- Neurodevelopmental Defects
- Skeletal Defects

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

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/?
B6.Cg-Psen1 Tg(APPSwe,tauP301L)1Lfa

behavior/neurological phenotype

abnormal behavior
- mutants attend less accurately to short, spatially unpredictable stimuli when the attentional demand of the task is high and also show a general tendency to make more perseverative responses than wild-type mice
- mutants initially respond as accurately as wild-type mice, however subsequently they fail to sustain their attention over the duration of the task, indicating reduced vigilance, or ability to sustain attention over a long period of time
- treatment of mice with the cholinesterase inhibitor donepezil results in an enhanced ability to sustain attention

References

Romberg C; Mattson MP; Mughal MR; Bussey TJ; Saksida LM. 2011. Impaired attention in the 3xTgAD mouse model of Alzheimer's disease: rescue by donepezil (Aricept). J Neurosci 31(9):3500-7PubMed: 21368062 MGI: J:170670

Additional - Psen1^tm1Mpm related

Additional - Tg(APPSwe,tauP301L)1Lfa related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- End Point Analysis:Psen1-EP
- QPCR:Generic APP human genomic or cDNA
- Standard PCR:Tg(TAU*P301S)#Elan
- Probe:Generic APP human genomic or cDNA
- Probe:Tg(APPSwe,tauP301L)1Lfa-Chr2-Probe-alt3
- 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/Product	Description	Price
	Hemizygous forTg(APPSwe,tauP301L)1Lfa and Heterozygous for Psen1<tm1Mpm>

Related Products and Services

Frozen Mouse Embryo	129S4.Cg-Tg(APPSwe tauP301L)1Lfa Psen1<tm1Mpm>/LfaJ	$2595.00
Frozen Mouse Embryo	129S4.Cg-Tg(APPSwe tauP301L)1Lfa Psen1<tm1Mpm>/LfaJ	$2595.00
Frozen Mouse Embryo	129S4.Cg-Tg(APPSwe tauP301L)1Lfa Psen1<tm1Mpm>/LfaJ	$3373.50
Frozen Mouse Embryo	129S4.Cg-Tg(APPSwe tauP301L)1Lfa Psen1<tm1Mpm>/LfaJ	$3373.50

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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

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

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Tg(APPSwe,tauP301L)1Lfa

Allele Symbol: Tg(APPSwe,tauP301L)1Lfa

Psen1tm1Mpm

Allele Symbol: Psen1tm1Mpm

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Phenotype

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

Genotype: Psen1tm1Mpm related

Mammalian Phenotype Terms by Genotype

Genotype: Psen1tm1Mpm/Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/?B6.Cg-Psen1 Tg(APPSwe,tauP301L)1Lfa

behavior/neurological phenotype

References

Additional - Psen1tm1Mpm related

Additional - Tg(APPSwe,tauP301L)1Lfa related

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

Related Products and Services

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

Psen1^tm1Mpm

Allele Symbol: Psen1^tm1Mpm

Genotype: Psen1^tm1Mpm related

Genotype: Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/?
B6.Cg-Psen1 Tg(APPSwe,tauP301L)1Lfa

Additional - Psen1^tm1Mpm related