Strain Name:
B6;129-Tg(APPSwe,tauP301L)1Lfa Psen1tm1Mpm/Mmjax
Stock Number:
034830-JAX
Citation ID:
RRID:MMRRC_034830-JAX
Other Names:

JAX Strain #004807 (B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax, 3xTg-AD.

Gene Information

Psen1tm1Mpm
Name: presenilin 1; targeted mutation 1, Mark P Mattson
Synonyms: PS1KI, PS1M146VKI-, PS-1 M146V KI, PS1M146V
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 12
Alteration at locus: Targeted Mutation
Psen1
Name: presenilin 1
Synonyms: PS1, S182, presenilin-1, PS-1, Ad3h
Type: Gene
Species: Mus musculus (mouse)
Chromosome: 12
Alteration at locus: Targeted Mutation
NCBI: 19164
VEGA: 12
HGNC: HGNC:9508
Homologene: 7186
Thy1
Name: thymus cell antigen 1, theta
Synonyms: Thy-1, CD90, Thy-1.2, Thy1.1, T25, Thy 1.2, Thy1.2
Type: Gene
Species: Mus musculus (mouse)
Chromosome: 9
Alteration at locus: Targeted Mutation
NCBI: 21838
Homologene: 4580
MAPT
Name: microtubule-associated protein tau
Type: Gene
Species: Homo sapiens (human)
Chromosome: 17
Alteration at locus: Targeted Mutation
APP
Name: amyloid beta precursor protein
Type: Gene
Species: Homo sapiens (human)
Chromosome: 21
Alteration at locus: Targeted Mutation
Tg(APPSwe,tauP301L)1Lfa
Name: transgene insertion 1, Frank M LaFerla
Synonyms: Tg(APP*Swe,MAPT*P301L)1Lfa
Type: Transgene
Species: Mus musculus (mouse)
Chromosome: unknown
Alteration at locus: Transgenic
Genetic Alterations
This line combines two alleles, Psen1tm1Mpm and Tg(APPSwe,tauP301L)1Lfa, which harbor several variants of the indicated genes. Transgene expression is driven by Thy1 (Thy1.2) regulatory elements.

HGVS nomenclature:

  • Psen1 allele (I145V, M146V):
    • Genbank RefSeq - mRNA: NM_001362271.1
    • Genbank RefSeq, protein:
    • Variant, nucleic acid level: c.433_436delinsGTTG
    • Variant, amino acid level, predicted: p.Ile145_Met146delinsValVal
      Check this variant: LUMC Mutalyzer

  • APP allele ("APPswe" or "Swedish Mutation" - K670N/M671L):
    • Genbank RefSeq - mRNA: NM_001198823.1
    • Genbank RefSeq, protein: NP_001185752.1
    • Variant, nucleic acid level: c.2010G>T and c.2011A>C = c.2010_2011inv
    • Variant, amino acid level, predicted: p.Lys670_Met671delinsAsnLeu (K670N/M671L)
      Check this variant: LUMC Mutalyzer

  • MAPT allele ("tauP301L"):
    • Genbank RefSeq - mRNA: NM_001123066.3 (Variant 6)
    • Genbank RefSeq, protein: NP_001116538.2
    • Variant, nucleic acid level: c.1907C>T
    • Variant, amino acid level, predicted: p.Pro636Leu
      Check this variant: LUMC Mutalyzer
      Note: The original description of "P301L" referenced a different (shorter) splice variant than used here, either NM_001203252.1 (Variant 8) or NM_005910.5 (Variant 2), which encode a proline at codon 301. Per HGVS nomenclature guidelines, the variant description was converted to reference the longest mRNA as shown above, which leads to P636L. Compare to NM_001203252.1:c.902C>T/p.Pro301Leu here, LUMC Mutalyzer.
Note: Current nomenclature rules would name the transgene "Tg(Thy1-APP*K670N,M671L,-MAPT*P636L)B1Lfa".
ES Cell Line
Psen1 allele: R1 derived from (129X1/SvJ x 129S1/Sv)F1-Kitl+
Phenotype

Homozygous: 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. A progressive increase in amyloid beta peptide deposition is observed, 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.

Hemizygous: Hemizygous transgenic phenotype is expected to be similar to homozygote phenotype.

Heterozygous: Heterozygote knockout phenotype is expected to be similar to the wild-type phenotype.

The donating investigator communicated in February 2014 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.

Mammalian Phenotype Terms
Allelic Composition: Psen1tm1Mpm/Psen1tm1Mpm (Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 )

Allelic Composition: Psen1tm1Mpm/Psen1tm1Shn (Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ )

Allelic Composition: Psen1tm1Mpm/Psen1tm1Pcw (Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6 )

MeSH Terms
  • Alzheimer Disease/drug therapy
  • Alzheimer Disease/genetics
  • Animals
  • Attention/drug effects
  • Attention/physiology
  • Conditioning, Operant/drug effects
  • Conditioning, Operant/physiology
  • Disease Models, Animal
  • Humans
  • Indans/administration & dosage
  • Indans/therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Piperidines/administration & dosage
  • Piperidines/therapeutic use
  • Alternative Splicing
  • Chromosomes, Human, Pair 17
  • DNA Mutational Analysis
  • Dementia/genetics
  • Exons
  • Female
  • Male
  • Mutation
  • Nerve Degeneration/genetics
  • Pedigree
  • RNA Splicing/genetics
  • tau Proteins/genetics
  • Alzheimer Disease/pathology
  • Amyloid beta-Peptides/genetics
  • Intracellular Fluid/metabolism
  • Neurofibrillary Tangles/genetics
  • Neurofibrillary Tangles/pathology
  • Plaque, Amyloid/genetics
  • Plaque, Amyloid/pathology
  • Synapses/genetics
  • Synapses/pathology
  • Glutamic Acid/pharmacology
  • Hippocampus/cytology
  • Kainic Acid/toxicity
  • Membrane Proteins/genetics
  • Membrane Proteins/physiology
  • Mice, Knockout
  • Neurons/drug effects
  • Presenilin-1
Strain Development
Single-cell embryos from mice bearing the presenilin PS1M146V knockin mutation on a mixed C7BL/6;129X1/SvJ;129S1/Sv genetic background (B6;129-Psen1tm1Mpm) were co-injected with two independent mutant human transgenes; amyloid-beta precursor protein (APP or "APPSwe") and microtubule-associated protein tau (MAPT or "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)). Both male and female 3xTg-AD mice on the mixed C57BL/6;129X1/SvJ;129S1/Sv genetic background were sent to the Repository and bred together to establish this colony.
Suggested Control Mice
B6129SF2/J (JAX Strain #101045) is an approximate control
  • Models for Human Disease
  • Neurobiology
Donor
Frank Laferla, Ph.D., University of California, Irvine.
Mark P. Mattson, Ph.D., Johns Hopkins University, School of Medicine.
Primary Reference

Romberg C, Mattson MP, Mughal MR, Bussey TJ, Saksida LM. Impaired attention in the 3xTgAD mouse model of Alzheimer's disease: rescue by donepezil (Aricept). J Neurosci. 2011 Mar 2;31(9):3500-7. (Medline PMID: 21368062)

Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaff E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon JM, Nowotny P, Che LK, Norton J, Morris JC, Reed LA, Trojanowski J, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd PR, Hayward N, Kwok JB, Schofield PR, Andreadis A, Snowden J, Craufurd D, Neary D, Owen F, Oostra BA, Hardy J, Goate A, van Swieten J, Mann D, Lynch T, Heutink P. Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Nature. 1998 Jun 18;393(6686):702-5. (Medline PMID: 9641683)

Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron. 2003 Jul 31;39(3):409-21. (Medline PMID: 12895417)

Guo Q, Fu W, Sopher BL, Miller MW, Ware CB, Martin GM, Mattson MP. Increasedvulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1mutant knock-in mice. Nat Med. 1999 Jan;5(1):101-6. (Medline PMID: 9883847)

Colony and Husbandry Information

When maintaining a live colony, mice that are homozygous for the Psen1 mutation and homozygous for the co-injected APPSwe and tauP301L transgenes (Tg(APPSwe,tauP301L)1Lfa) may be bred together.

Colony's Current Health Status Report

For more information about this colony's health status contact csmmrrc@jax.org
NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
Bred to Homozygosity
Yes

Order Request Information

Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at csmmrrc@jax.org for more details.

Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $) Units Notes
034830-JAX-MIX1-F
034830-JAX-MIX1-M
Homozygous Knockout / Homozygous Transgene female
Homozygous Knockout / Homozygous Transgene male
$140.00 / Non-Profit Per Mouse The csmmrrc@jax.org may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
034830-JAX-EMBRYO Cryo-preserved embryos $1,038.00 / Non-Profit Aliquot Approximate quantity2 : 20-40 embryos / aliquot
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.