Strain Detail Sheet

Strain Name    :

B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax

Stock Number :

034848-JAX

Other Names   :

This strain was formerly available as JaxMice stock number 8730. 5XFAD line Tg6799, FXFAD APP/PS1

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Transgene: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas
Name: transgene insertion 6799, Robert Vassar
Alteration at locus: Transgenic

Genetic Alterations:

Genotype Determination:

ES Cell Line:

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

Phenotype

Homozygote phenotype is expected to be similar to 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. 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 B6SJL F1 genetic background (MMRRC:034840), 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 (this strain) 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 does not carry the retinal degeneration allele Pde6brd1.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/-
        B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax


The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/-
        involves: C57BL/6 * SJL
  • behavior/neurological phenotype
    • abnormal spatial learning (MGI Ref ID J:112949)
      • by 4-5 months of age, defects in Y-maze alternation are detected in transgenic mice, indicating impaired spatial learning/memory
  • nervous system phenotype
    • abnormal hippocampus morphology (MGI Ref ID J:112949)
      • cortical layer 1 is significantly thinner than in control brains
      • abnormal subiculum morphology (MGI Ref ID J:112949)
        • neurons in subiculum are very pale, or absent
    • abnormal neuron morphology (MGI Ref ID J:112949)
      • some neurons contain intraneuronal aggregates and display disrupted morphology
      • decreased cerebral cortex pyramidal cell number (MGI Ref ID J:112949)
        • large neurons in cortical layer 5 are reduced in number
    • amyloid beta deposits (MGI Ref ID J:112949)
      • mice show Abeta42 deposits at 2 months of age; Abeta40 levels are lower in amyloid deposits; mice show robust intraneuronal amyloid deposition
      • amyloid deposition increases rapidly with increasing age
      • plaques appear first in deep cortical layers and in subiculum, and spread with age to fill most of cortex, subiculum and hippocampus; also, less numerous deposits are observed in thalamus, brainstem and olfactory bulb in older mice
    • brain infla mmation (MGI Ref ID J:112949)
      • transgenic mice display neuroinflammation
    • gliosis (MGI Ref ID J:112949)
      • microgliosis and astrogliosis is seen in plaque-bearing regions of the brain by 2 months of age; numbers of activated astrocytes and microglia increases with age
      • astrocytosis (MGI Ref ID J:112949)
    • neurodegeneration (MGI Ref ID J:112949)
      • synapse degeneration begins at 4 months of age, compared to nontransgenic controls, as shown by reduction in levels of synaptic markers; neurodeneration marker p25 level is ~150% of control at 9 and 12 months
  • immune system phenotype
    • brain inflammation (MGI Ref ID J:112949)
      • transgenic mice display neuroinflammation
  • other phenotype
    • amyloid beta deposits (MGI Ref ID J:112949)
      • mice show Abeta42 deposits at 2 months of age; Abeta40 levels are lower in amyloid deposits; mice show robust intraneuronal amyloid deposition
      • amyloid deposition increases rapidly with increasing age
      • plaques appear first in deep cortical layers and in subiculum, and spread with age to fill most of cortex, subiculum and hippocampus; also, less numerous deposits are observed in thalamus, brainstem and olfactory bulb in older mice
Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?
        involves: 129S4/SvJae * C57BL/6 * SJL
  • mortality/aging
    • premature death (MGI Ref ID J:169682)
      • impaired survival compared to wild-type mice
      • survive longer than transgenic mice that are also Apoa4 null
  • nervous system phenotype
    • amyloid beta deposits (MGI Ref ID J:169682)
    • neuron degeneration (MGI Ref ID J:169682)
  • other phenotype
    • amyloid beta deposits (MGI Ref ID J:169682)

Strain of Origin: C57/B6XSJL

Strain genetic background: B6.Cg

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 (B6/SJL)F1 for more than 10 generations with stable germ-line transmission and expression of both transgenes, demonstrating that these "5XFAD" mice breed as single transgenics. The mice were then backcrossed to C57BL/6J mice using a speed congenic protocol and the retinal degeneration allele Pde6brd1 was bred out of the strain. 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

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 C57BL/6J.

Health Status Report

Colony's Current Health Status Report

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

Appearance

Coat color:

Other:

Breeding

MMRRC Breeding System:

Breeding Scheme(s):

  • Wild-type female x Hemizygous male from the colony or reciprocal mating

Generation:

Overall Breeding Performance:

Reproductive Statistics

Viability and Fertility: Unknown

Average litter size:

Recommended wean age:

Order Request Information

Availability Level

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.

Conditions of Distribution [Including applicable technology transfer agreements]

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.

The donor or their institution limits the distribution to non-profit institutions only.

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 $)
Units Notes
034848-JAX-HEMI-FHemizygous female
034848-JAX-HEMI-MHemizygous male
034848-JAX-WT-FWild type female
034848-JAX-WT-MWild type male
$218.00
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.).

1 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.

2 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.

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

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 above). 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.



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.



The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

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