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.
Frank LaFerla, University of California, Irvine
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.
Currently there are no related genes or alleles for this strain.
When maintaining a live congenic colony, mice that are homozygous for the Psen1tm1Mpm allele and homozygous for the co-injected APPSwe and tauP301L transgenes, Tg(APPSwe,tauP301L)1Lfa, 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.
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.
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