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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Mutant Stock; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Hemizygote x F1 (Female x Male) 17-OCT-08 Mating System F1 x Hemizygote (Female x Male) 17-OCT-08 Species laboratory mouse Generation N11+N3 (05-FEB-09) Donating Investigator Robert Vassar, Northwestern University Description
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. 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. 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 homozygous/segregating for the retinal degeneration allele Pde6brd1.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. Of note, the APP transgene includes the 5' untranslated region and thus contains a putative interleukin-1beta translational enhancer element.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100012 B6SJLF1/J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of APP695
View Strains carrying other alleles of APP695 (9 strains)
Additional Web Information
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Phenotype
Phenotype Information
assigned by genotype
Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
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
- decreased pyramidal neuron number (MGI Ref ID J:112949)
- large neurons in layer 5 are reduced in number
- abnormal neuron morphology (MGI Ref ID J:112949)
- some neurons contain intraneuronal aggregates and display disrupted morphology
- decreased pyramidal neuron number (MGI Ref ID J:112949)
- large neurons in 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 inflammation (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
This mouse can be used to support research in many areas including:
APP695 relatedMouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease
APP and PSEN1 mutants
Presenilin mutants
strains expressing mutant APP
Neurodegeneration
Research Tools
Neurobiology Research
Neurobiology Research
Alzheimer's Disease
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas | ||
|---|---|---|---|
| Allele Name | transgene insertion 6799, Robert Vassar | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | 5XFAD; 5XFAD line Tg6799; Tg6799; | ||
| Mutation Made By | Robert Vassar, Northwestern University | ||
| Strain of Origin | (C57BL/6 x SJL)F1 | ||
| Expressed Gene | APP695, amyloid beta (A4) precursor protein (chimeric), mouse/human chimera | ||
| Expressed Gene | PSEN1, presenilin 1, human | ||
| Promoter | Thy1, thymus cell antigen 1, theta, mouse, laboratory | ||
| General Note | Three transgenic lines coexpressing the APP and PSEN1 proteins at high, medium and low levels, respectively designated Tg6799, Tg7031, and Tg7092, were propagated for analysis, most of which employed Tg6799. | ||
| Molecular Note | 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, L286V 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. [MGI Ref ID J:112949] [MGI Ref ID J:32213] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Generic Pde6b, Melt Curve Analysis
Generic Pde6b, Standard PCR
Generic Tg(APP) Melt Curve Analysis, Melt Curve Analysis
Tg(APP), Standard PCR
Tg(PSEN1), Melt Curve Analysis
Tg(PSEN1), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
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. 2006. 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 26(40):10129-40. [PubMed: 17021169] [MGI Ref ID J:112949]
Additional References
Zhao J; Fu Y; Yasvoina M; Shao P; Hitt B; O'Connor T; Logan S; Maus E; Citron M; Berry R; Binder L; Vassar R. 2007. Beta-site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: implications for Alzheimer's disease pathogenesis. J Neurosci 27(14):3639-49. [PubMed: 17409228] [MGI Ref ID J:119403]
Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas relatedKimura R; Ohno M. 2009. Impairments in remote memory stabilization precede hippocampal synaptic and cognitive failures in 5XFAD Alzheimer mouse model. Neurobiol Dis 33(2):229-35. [PubMed: 19026746] [MGI Ref ID J:144743]
Moechars D; Lorent K; De Strooper B; Dewachter I; Van Leuven F. 1996. Expression in brain of amyloid precursor protein mutated in the alpha-secretase site causes disturbed behavior, neuronal degeneration and premature death in transgenic mice. EMBO J 15(6):1265-74. [PubMed: 8635459] [MGI Ref ID J:32213]
Ohno M; Cole SL; Yasvoina M; Zhao J; Citron M; Berry R; Disterhoft JF; Vassar R. 2007. BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice. Neurobiol Dis 26(1):134-45. [PubMed: 17258906] [MGI Ref ID J:119002]
Zhao J; Fu Y; Yasvoina M; Shao P; Hitt B; O'Connor T; Logan S; Maus E; Citron M; Berry R; Binder L; Vassar R. 2007. Beta-site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: implications for Alzheimer's disease pathogenesis. J Neurosci 27(14):3639-49. [PubMed: 17409228] [MGI Ref ID J:119403]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous mice may be bred to B6SJLF1/J (Stock No. 100012). Mating System Hemizygote x F1 (Female x Male) 17-OCT-08 F1 x Hemizygote (Female x Male) 17-OCT-08 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $243.50 Female or Male Hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas
Pairs /Price (US dollars $) Pair Genotype $262.35 B6SJLF1/J (100012) x Hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas $261.05 Hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas x B6SJLF1/J (100012)
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $316.60 Female or Male Hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas
Pairs /Price (US dollars $) Pair Genotype $341.10 B6SJLF1/J (100012) x Hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas $339.40 Hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas x B6SJLF1/J (100012)
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100012 B6SJLF1/J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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