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.
Of note, 3xTg-AD mice are available on a B6;129 genetic background (Stock No. 004807 B6;129-Tg(APPSwe,tauP301L)1Lfa Psen1tm1Mpm/Mmjax), a 129S4 genetic background (Stock No. 031988 129S4.Cg-Tg(APPSwe,tauP301L)1Lfa Psen1tm1Mpm/LfaJ) or a C57BL/6J-congenic background (Stock No. 033930 B6.Cg-Tg(APPSwe,tauP301L)1Lfa Psen1tm1Mpm/2J).
Frank LaFerla, University of California, Irvine
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted | Psen1 | presenilin 1 |
Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
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.
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-Psen1tm1Mpm) 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-Psen1tm1Mpm 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.
Expressed Gene | APP, amyloid beta precursor protein, human |
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Expressed Gene | MAPT, microtubule associated protein tau, human |
Site of Expression |
Allele Name | targeted mutation 1, Mark P Mattson |
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Allele Type | Targeted |
Allele Synonym(s) | PS-1 M146V KI; PS1KI; PS1M146V; PS1M146VKI- |
Gene Symbol and Name | Psen1, presenilin 1 |
Gene Synonym(s) | |
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 |
Allele Name | transgene insertion 1, Frank M LaFerla |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | Tg(APP*Swe,MAPT*P301L)1Lfa |
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 Psentm1Mpm were generated by microinjection of the APP and MAPT transgenic constructs into single cell embryos harvested from mice homozygous for Psen1tm1Mpm. 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. |
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 [Psen1tm1Mpm on chromosome 12] may be bred together.
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.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Hemizygous forTg(APPSwe,tauP301L)1Lfa and Heterozygous for Psen1<tm1Mpm> |
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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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