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Strain Detail Sheet

Strain Name:
B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax
Stock Number:
034840-JAX
Citation ID:
RRID:MMRRC_034840-JAX
Other Names:
This strain is identical to RRID:IMSR_JAX:006554. 5XFAD line Tg6799, FXFAD APP/PS1

Strain Information

Gene Details

PSEN1
Name: presenilin 1 (Alzheimer disease 3)
Type: Gene
Species: Homo sapiens (human)
Chromosome: 14
APP
Name: amyloid beta precursor protein
Type: Gene
Species: Homo sapiens (human)
Chromosome: 21
Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas
Name: transgene insertion 6799, Robert Vassar
Synonyms: 5XFAD APP/PS1, Tg-5xFAD, Tg(APP*Swe*Fl*Lon,PSEN1*M146L*L286V)6799Vas, 5XFAD, 5XFAD line Tg6799, Tg6799
Type: Transgene
Species: Mus musculus (mouse)
Chromosome: unknown
Alteration at locus: Transgenic
Genetic Alterations

Four familial Alzheimer disease- (FAD-) associated mutations were introduced into a single human amyloid precursor protein cDNA: the "Swedish" double mutation (K670N/M671L); the "Florida" mutation (I716V); and the "London" mutation (V717I). Two FAD-associated mutations, M146L and L286V, likewise were introduced into a human presenilin 1 cDNA. Each cDNA was then cloned independently into the mouse thymus cell antigen 1 gene, replacing a segment that contains thymus-specific elements so that expression of the transgenes is targeted only to the brain. Equal molar amounts of the two transgenes were coinjected into pronuclei of single-celled embryos.

Genotype Determination

Strain Description

Phenotype
Homozygote: Phenotype is expected to be similar to the hemizygote phenotype.

Hemizygous: Mice are viable and fertile. These "5XFAD" transgenic mice overexpress both mutant human APP(695) with the Swedish (K670N, M671L), Florida (I716V), and London (V717I) Familial Alzheimer's Disease (FAD) mutations and human PS1 harboring two FAD mutations, M146L and L286V. The expression of both transgenes is regulated by neural-specific elements of the mouse Thy1 promoter to drive overexpression in the brain. Mice from this founder line have high APP expression correlating with high burden and accelerated accumulation of the 42 amino acid species of beta-amyloid (Abeta-42). 5XFAD mice generate Abeta-42 almost exclusively and rapidly accumulate massive cerebral levels. On the B6SJLF1 genetic background (this strain), intraneuronal Abeta-42 accumulation is observed starting at 1.5 months of age, just prior to amyloid deposition and gliosis, which begins at two months of age. On a congenic C57BL/6J genetic background (MMRRC:034848) it has been the observation of the MMRRC that this phenotype is not as robust as that demonstrated in the B6SJL hybrid background (view data). In addition, these mice have reduced synaptic marker protein levels, increased p25 levels, neuron loss, and memory impairment in the Y-maze test. 5XFAD transgenic mice rapidly recapitulate major features of Alzheimer's Disease amyloid pathology and may be useful models of intraneuronal Abeta-42 induced neurodegeneration and amyloid plaque formation.

This strain is segregating heterozygous/wildtype for the retinal degeneration allele Pde6brd1.

It should be noted that the SJL genetic background contains the Trem2S148E allele - a naturally occurring variant at position 48351151-48351152 on Chr 17 (rs108080490 and rs107649577; Ensembl GRCm38.p6). This TC-to-GA transition results in a serine to glutamic acid substitution at amino acid 148 (S148E). Because this model (MMRRC:34840) is maintained by backcrossing transgenic animals to B6SJLF1 at every generation, SJL content is segregating in the progeny of these animals. Mice produced from this cross could be genotypically heterozygous, homozygous, or wild-type for this locus. This variant may be of particular interest to those studying the role played by TREM2 in Alzheimer's Disease pathology.

NOTE: This 5XFAD transgene is also available on a C57BL/6J background (MMRRC:34848), which does not carry the Trem2S148E allele.
MeSH Terms
  • Alzheimer Disease/genetics
  • Alzheimer Disease/pathology
  • Amyloid beta-Peptides/genetics
  • Animals
  • Cell Count
  • Memory Disorders/genetics
  • Memory Disorders/pathology
  • Mice
  • Mice, Transgenic
  • Mutation
  • Nerve Degeneration/genetics
  • Nerve Degeneration/pathology
  • Neurofibrillary Tangles/genetics
  • Neurofibrillary Tangles/pathology
  • Neurons/pathology
  • Plaque, Amyloid/genetics
  • Plaque, Amyloid/pathology
Strain Development

A transgene was designed with a mutant human amyloid beta (A4) precursor protein (APP) cDNA sequence (altered to include the APP K670N/M671L (Swedish) + I716V (Florida) + V717I (London) Familial Alzheimer's Disease (FAD) mutations) inserted into exon 2 of the mouse Thy1 gene. A second transgene was designed with a mutant human presenilin 1 (Alzheimer disease 3) (PSEN1 or PS1) cDNA sequence (altered to include the PS1 M146L + L286V FAD mutations) inserted into exon 2 of the mouse Thy1 gene. Both transgenes were added together in equal proportions and co-injected into the pronuclei of single-cell "C57/B6XSJL" hybrid embryos. Founders from the highest APP expressing line (Tg6799) were bred with B6SJLF1/J (RRID:IMSR_JAX:100012) for more than 10 generations with stable germ-line transmission and expression of both transgenes, demonstrating that these "5XFAD" mice breed as single transgenics. Of note, the APP transgene includes the 5' untranslated region and thus contains a putative interleukin-1beta translational enhancer element.

Suggested Control Mice
Wild-type littermates

MMRRC Genetic QC

MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact csmmrrc@jax.org. Older strains may not have this information.

Research Applications

  • Models for Human Disease
  • Neurobiology

Strain Origin

Donor
Robert Vassar, Ph.D., Northwestern University
Primary Reference
Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, Berry R, Vassar R. Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation. J Neurosci. 2006 Oct 4;26(40):10129-40 (Medline PMID: 17021169)

Colony and Husbandry Information

Special Considerations

When maintaining a live colony, hemizygous mice may be bred to B6SJLF1/J (RRID:IMSR_JAX:100012). Males are very aggressive and are housed at lower densities to help reduce fighting as well as given alpha twists for enrichment. Breeders receive shacks and alpha twists to reduce aggression and decrease pre-wean loss.

This strain ships with remnant UID MiniMax microchips implanted subcutaneously in the back. For more information on these RFID chips, including our FAQ, please visit our Mouse Identification page.



Health Status Report

Colony's Current Health Status Report

For more information about this colony's health status contact csmmrrc@jax.org

Reproductive Statistics

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.
Viability and Fertility: Female Male Comments
Homozygotes are viable:
Homozygotes are fertile:
Hetero/Hemizygotes are fertile:
Age Reproductive Decline: Unknown Unknown
Bred to Homozygosity
Yes
Average litter size
First litters are smaller at 7, then averages 9-10 pups with subsequent litters
Recommended wean age
3 weeks

Order Request Information

Availability Level

Colony sized to accommodate the delivery of study cohorts. Please contact the distributing center directly for more details at csmmrrc@jax.org.

Conditions of Distribution

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

Fees

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 $)
*Shipping & Handling not included*		 Units Notes
034840-JAX-HET-F
034840-JAX-HET-M
034840-JAX-WT-F
034840-JAX-WT-M
Heterozygous / Hemizygous Female
Heterozygous / Hemizygous Male
Wild Type Female
Wild Type Male
 $147.00 / $147.00
Non-Profit / For-Profit		 Per Mouse The csmmrrc@jax.org may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
034840-JAX-EMBRYO Cryo-preserved embryos $1,090.00 / $1,090.00
Non-Profit / For-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.