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| This strain is now distributed by the Mutant Mouse Regional Resource Center. Please refer to the Mutant Mouse Regional Resource Center (MMRRC) for ordering information and strain details on (B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax
MMRRC Stock Number 034848. As a designated MMRRC center, The Jackson Laboratory will continue to distribute these mice at the same high health and quality standards but ordering is exclusively provided through the MMRRC. | |||||||||||||||||||
| 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. These 5XFAD transgenic mice rapidly recapitulate major features of Alzheimer's Disease amyloid pathology and may be useful models of intraneuronal Aβ-42 induced neurodegeneration and amyloid plaque formation. | |||||||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Former Names B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/J (Changed: 11-AUG-11 ) Type Congenic; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N6F2 (02-NOV-11)
Generation DefinitionsDonating Investigator IMR Colony, The Jackson Laboratory
Related Strains
Alzheimer's Disease Models
View Alzheimer's Disease Models (108 strains)
006554 B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax
006554 B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax
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
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
involves: C57BL/6 * SJL
- behavior/neurological phenotype
- abnormal spatial learning
- by 4-5 months of age, defects in Y-maze alternation are detected in transgenic mice, indicating impaired spatial learning/memory (MGI Ref ID J:112949)
- nervous system phenotype
- abnormal hippocampus morphology
- cortical layer 1 is significantly thinner than in control brains (MGI Ref ID J:112949)
- abnormal subiculum morphology
- neurons in subiculum are very pale, or absent (MGI Ref ID J:112949)
- abnormal neuron morphology
- some neurons contain intraneuronal aggregates and display disrupted morphology (MGI Ref ID J:112949)
- decreased cerebral cortex pyramidal cell number
- large neurons in cortical layer 5 are reduced in number (MGI Ref ID J:112949)
- amyloid beta deposits
- mice show Abeta42 deposits at 2 months of age; Abeta40 levels are lower in amyloid deposits; mice show robust intraneuronal amyloid deposition (MGI Ref ID J:112949)
- amyloid deposition increases rapidly with increasing age (MGI Ref ID J:112949)
- 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 (MGI Ref ID J:112949)
- brain inflammation
- transgenic mice display neuroinflammation (MGI Ref ID J:112949)
- gliosis
- 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 (MGI Ref ID J:112949)
- astrocytosis (MGI Ref ID J:112949)
- neurodegeneration
- 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 (MGI Ref ID J:112949)
- immune system phenotype
- brain inflammation
- transgenic mice display neuroinflammation (MGI Ref ID J:112949)
- other phenotype
- amyloid beta deposits
- mice show Abeta42 deposits at 2 months of age; Abeta40 levels are lower in amyloid deposits; mice show robust intraneuronal amyloid deposition (MGI Ref ID J:112949)
- amyloid deposition increases rapidly with increasing age (MGI Ref ID J:112949)
- 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 (MGI Ref ID J:112949)
Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?
involves: 129S4/SvJae * C57BL/6 * SJL
Genes & Alleles
Gene & Allele Information provided by MGI
| 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; FXFAD APP/PS1; Tg6799; | ||
| Mutation Made By | Robert Vassar, Northwestern University | ||
| Strain of Origin | (C57BL/6 x SJL)F1 | ||
| Expressed Gene | PSEN1, presenilin 1, human | ||
| Expressed Gene | APP695, amyloid beta (A4) precursor protein (chimeric), mouse/human chimera | ||
| 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 Tg(APP), Standard PCR
Tg(PSEN1), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
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
Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas relatedChristensen DZ; Bayer TA; Wirths O. 2009. Formic acid is essential for immunohistochemical detection of aggregated intraneuronal Abeta peptides in mouse models of Alzheimer's disease. Brain Res 1301:116-25. [PubMed: 19751708] [MGI Ref ID J:158791]
Cortes-Canteli M; Paul J; Norris EH; Bronstein R; Ahn HJ; Zamolodchikov D; Bhuvanendran S; Fenz KM; Strickland S. 2010. Fibrinogen and beta-amyloid association alters thrombosis and fibrinolysis: a possible contributing factor to Alzheimer's disease. Neuron 66(5):695-709. [PubMed: 20547128] [MGI Ref ID J:167873]
Cui Y; Huang M; He Y; Zhang S; Luo Y. 2011. Genetic Ablation of Apolipoprotein A-IV Accelerates Alzheimer's Disease Pathogenesis in a Mouse Model. Am J Pathol 178(3):1298-308. [PubMed: 21356380] [MGI Ref ID J:169682]
Devi L; Ohno M. 2010. Genetic reductions of beta-site amyloid precursor protein-cleaving enzyme 1 and amyloid-beta ameliorate impairment of conditioned taste aversion memory in 5XFAD Alzheimer's disease model mice. Eur J Neurosci 31(1):110-8. [PubMed: 20092558] [MGI Ref ID J:158363]
Devi L; Ohno M. 2012. Mitochondrial dysfunction and accumulation of the beta-secretase-cleaved C-terminal fragment of APP in Alzheimer's disease transgenic mice. Neurobiol Dis 45(1):417-24. [PubMed: 21933711] [MGI Ref ID J:179837]
Devi L; Ohno M. 2010. Phospho-eIF2alpha level is important for determining abilities of BACE1 reduction to rescue cholinergic neurodegeneration and memory defects in 5XFAD mice. PLoS One 5(9):e12974. [PubMed: 20886088] [MGI Ref ID J:165103]
Jawhar S; Wirths O; Schilling S; Graubner S; Demuth HU; Bayer TA. 2011. Overexpression of glutaminyl cyclase, the enzyme responsible for pyroglutamate A{beta} formation, induces behavioral deficits, and glutaminyl cyclase knock-out rescues the behavioral phenotype in 5XFAD mice. J Biol Chem 286(6):4454-60. [PubMed: 21148560] [MGI Ref ID J:169481]
Kimura R; Devi L; Ohno M. 2010. Partial reduction of BACE1 improves synaptic plasticity, recent and remote memories in Alzheimer's disease transgenic mice. J Neurochem 113(1):248-61. [PubMed: 20089133] [MGI Ref ID J:174832]
Kimura 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]
Mijatovic J; Piltonen M; Alberton P; Mannisto PT; Saarma M; Piepponen TP. 2011. Constitutive Ret signaling is protective for dopaminergic cell bodies but not for axonal terminals. Neurobiol Aging 32(8):1486-94. [PubMed: 19767128] [MGI Ref ID J:176716]
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. 2009. Failures to reconsolidate memory in a mouse model of Alzheimer's disease. Neurobiol Learn Mem 92(3):455-9. [PubMed: 19435612] [MGI Ref ID J:154421]
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]
Wirths O; Erck C; Martens H; Harmeier A; Geumann C; Jawhar S; Kumar S; Multhaup G; Walter J; Ingelsson M; Degerman-Gunnarsson M; Kalimo H; Huitinga I; Lannfelt L; Bayer TA. 2010. Identification of low molecular weight pyroglutamate A{beta} oligomers in Alzheimer disease: a novel tool for therapy and diagnosis. J Biol Chem 285(53):41517-24. [PubMed: 20971852] [MGI Ref ID J:167567]
Woo DC; Lee SH; Lee DW; Kim SY; Kim GY; Rhim HS; Choi CB; Kim HY; Lee CU; Choe BY. 2010. Regional metabolic alteration of Alzheimer's disease in mouse brain expressing mutant human APP-PS1 by 1H HR-MAS. Behav Brain Res 211(1):125-31. [PubMed: 20307581] [MGI Ref ID J:159678]
Zhang XM; Cai Y; Xiong K; Cai H; Luo XG; Feng JC; Clough RW; Struble RG; Patrylo PR; Yan XX. 2009. Beta-secretase-1 elevation in transgenic mouse models of Alzheimer's disease is associated with synaptic/axonal pathology and amyloidogenesis: implications for neuritic plaque development. Eur J Neurosci 30(12):2271-83. [PubMed: 20092570] [MGI Ref ID J:157228]
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
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