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Description
Strain Information
Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System See Colony Maintenance Species laboratory mouse Generation [N7p]+N4F3 (19-DEC-08) Donating Investigator David Borchelt, McKnight Brain Inst, Univ of Florida Description
Double transgenic mice are viable and fertile. At 6 months of age, double-transgenic mice show visible amyloid plaque deposition but are indistinguishable from nontransgenic animals in all cognitive measures. By 18 months, amyloid deposits were much higher in APPswe/PS1dE9 mice with statistically significant but mild decreases in cholinergic markers (cortex and hippocampus) and somatostatin levels (cortex). Performance of older double-transgenic mice is impaired in all cognitive tasks, and deficits in episodic-like memory tasks correlate with total amyloid-beta peptide loads in the brain.Development
Mutant amyloid precursor protein (APPswe) transgenic mice (line C3-3) express a chimeric mouse/human APP-695 with mutations linked to familial Alzheimers disease (KM 593/594 NL). The C3-3 line was backcrossed to C57BL/6J mice for 10 generations. Presenilin 1 (PSEN1) transgenic mice (line S-9) express human PSEN1 carrying the exon-9-deleted variant (PSEN1dE9) associated with familial Alzheimer's disease. Originally created on a hybrid strain background (C3H/HeJ;C57BL/6J), the S-9 line was backcrossed to C57BL/6J for six generations. Both are under the control of the mouse prion protein (PrP) promoter, directing transgene expression predominantly to CNS neurons. APPswe/PS1dE9 double transgenic mice were produced by mating APP-695 line C3-3 males to PS1dE9 line S-9 females, and then backcrossing double transgenic males to C57BL/6J mice for >10 generations before arriving at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Tg(APP695)3Dbo allele
003378 B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J 003375 C3B6-Tg(APP695)3Dbo/J View Strains carrying Tg(APP695)3Dbo (2 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
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0
involves: C3H/HeJ * C57BL/6J
- nervous system phenotype
- amyloid beta deposits (MGI Ref ID J:104236)
- at 7 months of age, mice exhibit amyloid plaques in the hippocampus and cortex
- develops diffuse, compact, birefringent congophilic plaques in cortex and hippocampus
- ratio of amyloid beta peptide 40:42 is 0.75:1
- 150% increase in amyloid beta peptide 42
- other phenotype
- amyloid beta deposits (MGI Ref ID J:104236)
- at 7 months of age, mice exhibit amyloid plaques in the hippocampus and cortex
- develops diffuse, compact, birefringent congophilic plaques in cortex and hippocampus
- ratio of amyloid beta peptide 40:42 is 0.75:1
- 150% increase in amyloid beta peptide 42
Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0
involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J
- behavior/neurological phenotype
- *normal* behavior/neurological phenotype (MGI Ref ID J:123534)
- abnormal spatial learning (MGI Ref ID J:123534)
- mice travel shorter distance in open-field and show less activity or excursions into central area; mice remain near periphery of apparatus rather than entering open center of field
- abnormal spatial reference memory (MGI Ref ID J:123534)
- 16-18 month-old mice swim farther to find platform and spend less time in platform vicinity than controls
- nervous system phenotype
- amyloid beta deposits (MGI Ref ID J:123534)
- one month following neuron injection with virus expressing short hairpin RNA to silence Bace1, there is a 38% reduction in amyloid beta burden in hippocampus compared to uninjected hippocampus
- other phenotype
- amyloidosis (MGI Ref ID J:123534)
- mice display amyloid beta aggregates at 12 and 20 months
- amyloid beta deposits (MGI Ref ID J:123534)
- one month following neuron injection with virus expressing short hairpin RNA to silence Bace1, there is a 38% reduction in amyloid beta burden in hippocampus compared to uninjected hippocampus
Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0
Background Not Specified
- nervous system phenotype
- abnormal amacrine cell morphology (MGI Ref ID J:139070)
- distribution of amacrine cell processes is disrupted as determined by syntaxin 1 staining
- abnormal microglial cell morphology (MGI Ref ID J:139070)
- increase in microglial cell activity in retina is observed in 12-15 month old transgenics
- microglia processes in the retina are thicker and display a dendritic-like appearance as compared to control
- microglia density, but not cell body size, is increased in transgenics
- amyloid beta deposits (MGI Ref ID J:139070)
- thioflavine-S positive plaques are observed in the retina beginning at 12 months of age
- plaques have radial branches with a central core
- plaque size ranges from 5-20 um, larger plaques are observed at 15-16 months
- plaques appear earlier in females than in males and increase in number over time
- 100% of females and 75% of males have plaques in retina by 15-16 months
- vision/eye phenotype
- abnormal eye electrophysiology (MGI Ref ID J:139070)
- amplitudes of a and b waves are decreased in 12-16 month old mice when tested at lower light intensity, but not a higher intensity
- latency and implicit time as determined by ERG measurement are similar to control
- abnormal retina morphology (MGI Ref ID J:139070)
- thioflavine-S positive plaques are observed in the retina beginning at 12 months of age
- most plaques (34.7% and 41% respectively) are found in the inner and outer plexiform layers
- thickness of the retinal nuclear layers is similar to control, suggesting that there is no obvious neuronal cell loss
- abnormal amacrine cell morphology (MGI Ref ID J:139070)
- distribution of amacrine cell processes is disrupted as determined by syntaxin 1 staining
- abnormal retinal inner plexiform layer morphology (MGI Ref ID J:139070)
- thioflavine-S positive plaques are first observed in females in the IPL at 12 months
- plaques are first observed in males at 13 months
- plaques are embedded within IPL cholinergic bands
- abnormal retinal outer plexiform layer morphology (MGI Ref ID J:139070)
- thioflavine-S positive plaques are first observed in females in the OPL at 12 months
- plaques are first observed in males at 13 months
- immune system phenotype
- abnormal microglial cell morphology (MGI Ref ID J:139070)
- increase in microglial cell activity in retina is observed in 12-15 month old transgenics
- microglia processes in the retina are thicker and display a dendritic-like appearance as compared to control
- microglia density, but not cell body size, is increased in transgenics
- other phenotype
- amyloid beta deposits (MGI Ref ID J:139070)
- thioflavine-S positive plaques are observed in the retina beginning at 12 months of age
- plaques have radial branches with a central core
- plaque size ranges from 5-20 um, larger plaques are observed at 15-16 months
- plaques appear earlier in females than in males and increase in number over time
- 100% of females and 75% of males have plaques in retina by 15-16 months
- hematopoietic system phenotype
- abnormal microglial cell morphology (MGI Ref ID J:139070)
- increase in microglial cell activity in retina is observed in 12-15 month old transgenics
- microglia processes in the retina are thicker and display a dendritic-like appearance as compared to control
- microglia density, but not cell body size, is increased in transgenics
This mouse can be used to support research in many areas including:
Tg(APP695)3Dbo relatedNeurobiology Research
Alzheimer's Disease
APP and PSEN1 mutants
Presenilin mutants
strains expressing mutant APP
Behavioral and Learning Defects
Mouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease
Neurodegeneration
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(APP695)3Dbo | ||
|---|---|---|---|
| Allele Name | transgene insertion 3, David R Borchelt | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | APP695; APP695swe; APPswe; Mo/HuAPPswe; line C3-3; | ||
| Mutation Made By | David Borchelt, McKnight Brain Inst, Univ of Florida | ||
| Strain of Origin | (C57BL/6J x C3H/HeJ)F2 | ||
| Expressed Gene | APP695, amyloid beta (A4) precursor protein (chimeric), mouse/human chimera | ||
| Promoter | Prnp, prion protein, mouse, laboratory | ||
| General Note |
Three transgenic lines were generated and designated by the authors lines Q2-2, E1-2 (Tg(Prnp-App/APPswe)E1-2Dbo) and C3-3. This line was generated from foundernumber C3-3. Transgenic mice develop amyloid deposits in brain tissue by 18-20 months of age. Transgenic mice that are also transgenic for Tg(PSEN1)5Dboexpress both human presenilin 1 (A246E variant) and a chimeric amyloid precursor protein (APPSwe) under direction of the mouse prion protein promoter. Elevated levels of the AB1-42(43) peptide are detected in brain homogenates. By nine months of age, histological examination of brain tissue from these mice reveals numerous amyloid deposits resembling those observed in the brains of patients with Alzheimer's disease (AD). The number of amyloid deposits increases dramatically between the ages of 10 and 12 months. | ||
| Molecular Note | The transgene is composed of a cDNA encoding a chimeric APP protein regulated by the mouse prion promoter. The chimeric APP molecule was created by replacing sequences encoding the Abeta domain of a 695 amino acid isoform of the murine sequence with the cognate sequences of the human gene (mutations K595N, M596L). The human mutations are found in familial Alzheimer's disease. Transgene expression was observed in the brain and heart by Western blot analysis using a monoclonal antibody recognizing the human Abeta region. [MGI Ref ID J:80782] | ||
| Allele Symbol | Tg(PSEN1dE9)S9Dbo | ||
| Allele Name | transgene insertion S9, David R Borchelt | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | PS1 deltaE9; PS1 transgene (line S-9); PS1-deltaE9; PS1dE9 transgene; PS1deltaE9 (line S-9); deltaE9; huPS1deltaE9; line S-9; | ||
| Mutation Made By | David Borchelt, McKnight Brain Inst, Univ of Florida | ||
| Strain of Origin | (C57BL/6J x C3H/HeJ)F2 | ||
| Expressed Gene | PSEN1, presenilin 1, human | ||
| General Note |
The deltaE9 PSEN1 protein variant fails to undergo endoproteolysis in cultured lymphoblasts from an affected human carrier and instead accumulates as the full-length, 40 kDa mutant protein (J:34323). Similarly, immunoblotting of of cortical and hippocampal extracts from transgenic mice under conditions that distinguish mouse and human full-length PSEN1 and their endoproteolytic derivatives demonstrates failure of thetransgenic protein to undergo endoproteolysis. (J:104147) The amount of full-length mutant human PSEN1 in brains of deltaE9 PSEN1 transgenic mice exceeds by ~60% the cumulative amount of the full-length human PSEN1 and its N-terminal derivative in brains of transgenic mice expressing wild-type human PSEN1. (J:104147) | ||
| Molecular Note | The coding sequence of the transgene is derived from the cDNA of the familial Alzheimer disease- (FAD-) associated deltaE9 variant of human presenilin 1, which has a splice acceptor mutation upstream of exon 9 that results in a protein lacking amino acids 290-319. The mutant cDNA replaces the coding region of the mouse prion protein (Prp) gene in a construct that contains ~6 kb of genomic DNA upstream of the primary PRP translation start site and includes the noncoding first exon and first intron and, following the inserted PSEN1 sequence, ~3 kb of 3' untranslated sequence; this construct has been shown to drive expression in both neurons and glial cells of the central nervous system (CNS). [MGI Ref ID J:104147] [MGI Ref ID J:34323] [MGI Ref ID J:80782] | ||
Genotyping
Genotyping Information
Genotyping Protocols
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)
Savonenko A; Xu GM; Melnikova T; Morton JL; Gonzales V; Wong MP; Price DL; Tang F; Markowska AL; Borchelt DR. 2005. Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities. Neurobiol Dis 18(3):602-17. [PubMed: 15755686] [MGI Ref ID J:104236]
Additional References
Verret L; Jankowsky JL; Xu GM; Borchelt DR; Rampon C. 2007. Alzheimer's-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis. J Neurosci 27(25):6771-80. [PubMed: 17581964] [MGI Ref ID J:122001]
Tg(APP695)3Dbo relatedTg(PSEN1dE9)S9Dbo relatedBoissonneault V; Plante I; Rivest S; Provost P. 2009. MicroRNA-298 and microRNA-328 regulate expression of mouse beta-amyloid precursor protein-converting enzyme 1. J Biol Chem 284(4):1971-81. [PubMed: 18986979] [MGI Ref ID J:146980]
Borchelt DR; Davis J; Fischer M; Lee MK; Slunt HH; Ratovitsky T; Regard J; Copeland NG; Jenkins NA; Sisodia SS; Price DL. 1996. A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet Anal 13(6):159-63. [PubMed: 9117892] [MGI Ref ID J:80782]
Borchelt DR; Ratovitski T; van Lare J; Lee MK; Gonzales V; Jenkins NA; Copeland NG; Price DL; Sisodia SS. 1997. Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron 19(4):939-45. [PubMed: 9354339] [MGI Ref ID J:43788]
Borchelt DR; Thinakaran G; Eckman CB; Lee MK; Davenport F; Ratovitsky T; Prada CM; Kim G; Seekins S; Yager D; Slunt HH; Wang R; Seeger M; Levey AI; Gandy SE; Copeland NG; Jenkins NA; Price DL; Younkin SG; Sisodia SS. 1996. Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron 17(5):1005-13. [PubMed: 8938131] [MGI Ref ID J:80882]
Cai D; Zhong M; Wang R; Netzer WJ; Shields D; Zheng H; Sisodia SS; Foster DA; Gorelick FS; Xu H; Greengard P. 2006. Phospholipase D1 corrects impaired betaAPP trafficking and neurite outgrowth in familial Alzheimer's disease-linked presenilin-1 mutant neurons. Proc Natl Acad Sci U S A 103(6):1936-40. [PubMed: 16449385] [MGI Ref ID J:106075]
Dodson SE; Andersen OM; Karmali V; Fritz JJ; Cheng D; Peng J; Levey AI; Willnow TE; Lah JJ. 2008. Loss of LR11/SORLA enhances early pathology in a mouse model of amyloidosis: evidence for a proximal role in Alzheimer's disease. J Neurosci 28(48):12877-86. [PubMed: 19036982] [MGI Ref ID J:142501]
El-Amouri SS; Zhu H; Yu J; Marr R; Verma IM; Kindy MS. 2008. Neprilysin: an enzyme candidate to slow the progression of Alzheimer's disease. Am J Pathol 172(5):1342-54. [PubMed: 18403590] [MGI Ref ID J:134308]
Filali M; Lalonde R; Rivest S. 2008. Cognitive and non-cognitive behaviors in an APPswe/PS1 bigenic model of Alzheimer's disease. Genes Brain Behav :. [PubMed: 19077180] [MGI Ref ID J:142183]
Garcia-Alloza M; Dodwell SA; Meyer-Luehmann M; Hyman BT; Bacskai BJ. 2006. Plaque-derived oxidative stress mediates distorted neurite trajectories in the Alzheimer mouse model. J Neuropathol Exp Neurol 65(11):1082-9. [PubMed: 17086105] [MGI Ref ID J:120918]
Gureviciene I; Ikonen S; Gurevicius K; Sarkaki A; van Groen T; Pussinen R; Ylinen A; Tanila H. 2004. Normal induction but accelerated decay of LTP in APP + PS1 transgenic mice. Neurobiol Dis 15(2):188-95. [PubMed: 15006688] [MGI Ref ID J:128772]
Iivonen H; Nurminen L; Harri M; Tanila H; Puolivali J. 2003. Hypothermia in mice tested in Morris water maze. Behav Brain Res 141(2):207-13. [PubMed: 12742257] [MGI Ref ID J:130974]
Jankowsky JL; Fadale DJ; Anderson J; Xu GM; Gonzales V; Jenkins NA; Copeland NG; Lee MK; Younkin LH; Wagner SL; Younkin SG; Borchelt DR. 2004. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13(2):159-70. [PubMed: 14645205] [MGI Ref ID J:87691]
Jankowsky JL; Melnikova T; Fadale DJ; Xu GM; Slunt HH; Gonzales V; Younkin LH; Younkin SG; Borchelt DR; Savonenko AV. 2005. Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer's disease. J Neurosci 25(21):5217-24. [PubMed: 15917461] [MGI Ref ID J:98541]
Jankowsky JL; Slunt HH; Gonzales V; Jenkins NA; Copeland NG; Borchelt DR. 2004. APP processing and amyloid deposition in mice haplo-insufficient for presenilin 1. Neurobiol Aging 25(7):885-92. [PubMed: 15212842] [MGI Ref ID J:102351]
Kalesnykas G; Roschier U; Puolivali J; Wang J; Miettinen R. 2005. The effect of aging on the subcellular distribution of estrogen receptor-alpha in the cholinergic neurons of transgenic and wild-type mice. Eur J Neurosci 21(5):1437-42. [PubMed: 15813954] [MGI Ref ID J:101077]
Laird FM; Cai H; Savonenko AV; Farah MH; He K; Melnikova T; Wen H; Chiang HC; Xu G; Koliatsos VE; Borchelt DR; Price DL; Lee HK; Wong PC. 2005. BACE1, a major determinant of selective vulnerability of the brain to amyloid-beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions. J Neurosci 25(50):11693-709. [PubMed: 16354928] [MGI Ref ID J:123534]
Lazarov O; Morfini GA; Pigino G; Gadadhar A; Chen X; Robinson J; Ho H; Brady ST; Sisodia SS. 2007. Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer's disease-linked mutant presenilin 1. J Neurosci 27(26):7011-20. [PubMed: 17596450] [MGI Ref ID J:122975]
Lee GD; Aruna JH; Barrett PM; Lei DL; Ingram DK; Mouton PR. 2005. Stereological analysis of microvascular parameters in a double transgenic model of Alzheimer's disease. Brain Res Bull 65(4):317-22. [PubMed: 15811597] [MGI Ref ID J:135436]
Lesuisse C; Xu G; Anderson J; Wong M; Jankowsky J; Holtz G; Gonzalez V; Wong PC; Price DL; Tang F; Wagner S; Borchelt DR. 2001. Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice. Hum Mol Genet 10(22):2525-37. [PubMed: 11709540] [MGI Ref ID J:72987]
Li G; Zou L; Jack CR Jr; Yang Y; Yang ES. 2007. Neuroprotective effect of Coenzyme Q10 on ischemic hemisphere in aged mice with mutations in the amyloid precursor protein. Neurobiol Aging 28(6):877-82. [PubMed: 16806588] [MGI Ref ID J:121939]
Li L; Zhang X; Yang D; Luo G; Chen S; Le W. 2009. Hypoxia increases Abeta generation by altering beta- and gamma-cleavage of APP. Neurobiol Aging 30(7):1091-8. [PubMed: 18063223] [MGI Ref ID J:152965]
Liu L; Ikonen S; Heikkinen T; Heikkila M; Puolivali J; van Groen T; Tanila H. 2002. Effects of fimbria-fornix lesion and amyloid pathology on spatial learning and memory in transgenic APP+PS1 mice. Behav Brain Res 134(1-2):433-45. [PubMed: 12191831] [MGI Ref ID J:129807]
Liu L; Tapiola T; Herukka SK; Heikkila M; Tanila H. 2003. Abeta levels in serum, CSF and brain, and cognitive deficits in APP + PS1 transgenic mice. Neuroreport 14(1):163-6. [PubMed: 12544850] [MGI Ref ID J:89843]
Liu Y; Yoo MJ; Savonenko A; Stirling W; Price DL; Borchelt DR; Mamounas L; Lyons WE; Blue ME; Lee MK. 2008. Amyloid pathology is associated with progressive monoaminergic neurodegeneration in a transgenic mouse model of Alzheimer's disease. J Neurosci 28(51):13805-14. [PubMed: 19091971] [MGI Ref ID J:143521]
Lopez JR; Lyckman A; Oddo S; Laferla FM; Querfurth HW; Shtifman A. 2008. Increased intraneuronal resting [Ca2+] in adult Alzheimer's disease mice. J Neurochem 105(1):262-71. [PubMed: 18021291] [MGI Ref ID J:141555]
Oh ES; Savonenko AV; King JF; Fangmark Tucker SM; Rudow GL; Xu G; Borchelt DR; Troncoso JC. 2009. Amyloid precursor protein increases cortical neuron size in transgenic mice. Neurobiol Aging 30(8):1238-44. [PubMed: 18304698] [MGI Ref ID J:152955]
Ojala J; Alafuzoff I; Herukka SK; van Groen T; Tanila H; Pirttila T. 2009. Expression of interleukin-18 is increased in the brains of Alzheimer's disease patients. Neurobiol Aging 30(2):198-209. [PubMed: 17658666] [MGI Ref ID J:145816]
Perez SE; Dar S; Ikonomovic MD; DeKosky ST; Mufson EJ. 2007. Cholinergic forebrain degeneration in the APPswe/PS1DeltaE9 transgenic mouse. Neurobiol Dis 28(1):3-15. [PubMed: 17662610] [MGI Ref ID J:134818]
Perez SE; Lazarov O; Koprich JB; Chen EY; Rodriguez-Menendez V; Lipton JW; Sisodia SS; Mufson EJ. 2005. Nigrostriatal dysfunction in familial Alzheimer's disease-linked APPswe/PS1DeltaE9 transgenic mice. J Neurosci 25(44):10220-9. [PubMed: 16267229] [MGI Ref ID J:102362]
Perez SE; Lumayag S; Kovacs B; Mufson EJ; Xu S. 2008. {beta}-Amyloid Deposition and Functional Impairment in the Retina of the APPswe/PS1{Delta}E9 Transgenic Mouse Model of Alzheimer's Disease. Invest Ophthalmol Vis Sci :. [PubMed: 18791173] [MGI Ref ID J:139070]
Pistell PJ; Zhu M; Ingram DK. 2008. Acquisition of conditioned taste aversion is impaired in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer's disease. Neuroscience 152(3):594-600. [PubMed: 18304749] [MGI Ref ID J:135640]
Popovic M; Caballero-Bleda M; Kadish I; Van Groen T. 2008. Subfield and layer-specific depletion in calbindin-D28K, calretinin and parvalbumin immunoreactivity in the dentate gyrus of amyloid precursor protein/presenilin 1 transgenic mice. Neuroscience 155(1):182-91. [PubMed: 18583063] [MGI Ref ID J:140778]
Richard KL; Filali M; Prefontaine P; Rivest S. 2008. Toll-like receptor 2 acts as a natural innate immune receptor to clear amyloid beta 1-42 and delay the cognitive decline in a mouse model of Alzheimer's disease. J Neurosci 28(22):5784-93. [PubMed: 18509040] [MGI Ref ID J:136387]
Savonenko AV; Xu GM; Price DL; Borchelt DR; Markowska AL. 2003. Normal cognitive behavior in two distinct congenic lines of transgenic mice hyperexpressing mutant APP SWE. Neurobiol Dis 12(3):194-211. [PubMed: 12742740] [MGI Ref ID J:109847]
Simard AR; Soulet D; Gowing G; Julien JP; Rivest S. 2006. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron 49(4):489-502. [PubMed: 16476660] [MGI Ref ID J:107605]
Simpson RJ. 1992. Effect of hypoxic exposure on iron absorption in heterozygous hypotransferrinaemic mice. Ann Hematol 65(6):260-4. [PubMed: 1457587] [MGI Ref ID J:12201]
Soderman A; Thomsen MS; Hansen HH; Nielsen EO; Jensen MS; West MJ; Mikkelsen JD. 2008. The nicotinic alpha7 acetylcholine receptor agonist ssr180711 is unable to activate limbic neurons in mice overexpressing human amyloid-beta1-42. Brain Res 1227:240-7. [PubMed: 18619425] [MGI Ref ID J:139987]
Stokin GB; Lillo C; Falzone TL; Brusch RG; Rockenstein E; Mount SL; Raman R; Davies P; Masliah E; Williams DS; Goldstein LS. 2005. Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science 307(5713):1282-8. [PubMed: 15731448] [MGI Ref ID J:96346]
Szapacs ME; Numis AL; Andrews AM. 2004. Late onset loss of hippocampal 5-HT and NE is accompanied by increases in BDNF protein expression in mice co-expressing mutant APP and PS1. Neurobiol Dis 16(3):572-80. [PubMed: 15262269] [MGI Ref ID J:131666]
Tang J; Song M; Wang Y; Fan X; Xu H; Bai Y. 2009. Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APP(swe)/PS1(DeltaE9) transgenic mouse model of Alzheimer's disease. Biochem Biophys Res Commun 385(3):341-5. [PubMed: 19463786] [MGI Ref ID J:150675]
Turdi S; Guo R; Huff AF; Wolf EM; Culver B; Ren J. 2009. Cardiomyocyte contractile dysfunction in the APPswe/PS1dE9 mouse model of Alzheimer's disease. PLoS One 4(6):e6033. [PubMed: 19551139] [MGI Ref ID J:150191]
Vepsalainen S; Hiltunen M; Helisalmi S; Wang J; van Groen T; Tanila H; Soininen H. 2008. Increased expression of Abeta degrading enzyme IDE in the cortex of transgenic mice with Alzheimer's disease-like neuropathology. Neurosci Lett 438(2):216-20. [PubMed: 18455870] [MGI Ref ID J:136710]
Verret L; Jankowsky JL; Xu GM; Borchelt DR; Rampon C. 2007. Alzheimer's-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis. J Neurosci 27(25):6771-80. [PubMed: 17581964] [MGI Ref ID J:122001]
Wang J; Ikonen S; Gurevicius K; Van Groen T; Tanila H. 2003. Altered auditory-evoked potentials in mice carrying mutated human amyloid precursor protein and presenilin-1 transgenes. Neuroscience 116(2):511-7. [PubMed: 12559106] [MGI Ref ID J:128594]
Wang J; Ikonen S; Gurevicius K; van Groen T; Tanila H. 2002. Alteration of cortical EEG in mice carrying mutated human APP transgene. Brain Res 943(2):181-90. [PubMed: 12101040] [MGI Ref ID J:78111]
Wang J; Tanila H; Puolivali J; Kadish I; van Groen T. 2003. Gender differences in the amount and deposition of amyloidbeta in APPswe and PS1 double transgenic mice. Neurobiol Dis 14(3):318-27. [PubMed: 14678749] [MGI Ref ID J:100956]
Xiang Z; Ho L; Valdellon J; Borchelt D; Kelley K; Spielman L; Aisen PS; Pasinetti GM. 2002. Cyclooxygenase (COX)-2 and cell cycle activity in a transgenic mouse model of Alzheimer's disease neuropathology. Neurobiol Aging 23(3):327-34. [PubMed: 11959394] [MGI Ref ID J:100961]
Yan P; Bero AW; Cirrito JR; Xiao Q; Hu X; Wang Y; Gonzales E; Holtzman DM; Lee JM. 2009. Characterizing the appearance and growth of amyloid plaques in APP/PS1 mice. J Neurosci 29(34):10706-14. [PubMed: 19710322] [MGI Ref ID J:152312]
Zhou XW; Gustafsson JA; Tanila H; Bjorkdahl C; Liu R; Winblad B; Pei JJ. 2008. Tau hyperphosphorylation correlates with reduced methylation of protein phosphatase 2A. Neurobiol Dis 31(3):386-94. [PubMed: 18586097] [MGI Ref ID J:138611]
van Groen T; Liu L; Ikonen S; Kadish I. 2003. Diffuse amyloid deposition, but not plaque number, is reduced in amyloid precursor protein/presenilin 1 double-transgenic mice by pathway lesions. Neuroscience 119(4):1185-97. [PubMed: 12831872] [MGI Ref ID J:100957]
Borchelt DR; Davis J; Fischer M; Lee MK; Slunt HH; Ratovitsky T; Regard J; Copeland NG; Jenkins NA; Sisodia SS; Price DL. 1996. A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet Anal 13(6):159-63. [PubMed: 9117892] [MGI Ref ID J:80782]
Choi SH; Veeraraghavalu K; Lazarov O; Marler S; Ransohoff RM; Ramirez JM; Sisodia SS. 2008. Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation. Neuron 59(4):568-80. [PubMed: 18760694] [MGI Ref ID J:149876]
Dodson SE; Andersen OM; Karmali V; Fritz JJ; Cheng D; Peng J; Levey AI; Willnow TE; Lah JJ. 2008. Loss of LR11/SORLA enhances early pathology in a mouse model of amyloidosis: evidence for a proximal role in Alzheimer's disease. J Neurosci 28(48):12877-86. [PubMed: 19036982] [MGI Ref ID J:142501]
El-Amouri SS; Zhu H; Yu J; Marr R; Verma IM; Kindy MS. 2008. Neprilysin: an enzyme candidate to slow the progression of Alzheimer's disease. Am J Pathol 172(5):1342-54. [PubMed: 18403590] [MGI Ref ID J:134308]
Garcia-Alloza M; Dodwell SA; Meyer-Luehmann M; Hyman BT; Bacskai BJ. 2006. Plaque-derived oxidative stress mediates distorted neurite trajectories in the Alzheimer mouse model. J Neuropathol Exp Neurol 65(11):1082-9. [PubMed: 17086105] [MGI Ref ID J:120918]
Jankowsky JL; Fadale DJ; Anderson J; Xu GM; Gonzales V; Jenkins NA; Copeland NG; Lee MK; Younkin LH; Wagner SL; Younkin SG; Borchelt DR. 2004. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13(2):159-70. [PubMed: 14645205] [MGI Ref ID J:87691]
Jankowsky JL; Slunt HH; Ratovitski T; Jenkins NA; Copeland NG; Borchelt DR. 2001. Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol Eng 17(6):157-65. [PubMed: 11337275] [MGI Ref ID J:78664]
Jankowsky JL; Younkin LH; Gonzales V; Fadale DJ; Slunt HH; Lester HA; Younkin SG; Borchelt DR. 2007. Rodent A beta modulates the solubility and distribution of amyloid deposits in transgenic mice. J Biol Chem 282(31):22707-20. [PubMed: 17556372] [MGI Ref ID J:124804]
Kuchibhotla KV; Goldman ST; Lattarulo CR; Wu HY; Hyman BT; Bacskai BJ. 2008. Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks. Neuron 59(2):214-25. [PubMed: 18667150] [MGI Ref ID J:145474]
Laird FM; Cai H; Savonenko AV; Farah MH; He K; Melnikova T; Wen H; Chiang HC; Xu G; Koliatsos VE; Borchelt DR; Price DL; Lee HK; Wong PC. 2005. BACE1, a major determinant of selective vulnerability of the brain to amyloid-beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions. J Neurosci 25(50):11693-709. [PubMed: 16354928] [MGI Ref ID J:123534]
Lazarov O; Morfini GA; Pigino G; Gadadhar A; Chen X; Robinson J; Ho H; Brady ST; Sisodia SS. 2007. Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer's disease-linked mutant presenilin 1. J Neurosci 27(26):7011-20. [PubMed: 17596450] [MGI Ref ID J:122975]
Lee GD; Aruna JH; Barrett PM; Lei DL; Ingram DK; Mouton PR. 2005. Stereological analysis of microvascular parameters in a double transgenic model of Alzheimer's disease. Brain Res Bull 65(4):317-22. [PubMed: 15811597] [MGI Ref ID J:135436]
Lee MK; Borchelt DR; Kim G; Thinakaran G; Slunt HH; Ratovitski T; Martin LJ; Kittur A; Gandy S; Levey AI; Jenkins N; Copeland N; Price DL; Sisodian SS. 1997. Hyperaccumulation of FAD-linked presenilin 1 variants in vivo Nat Med 3(7):756-60. [PubMed: 9212102] [MGI Ref ID J:104147]
Lesuisse C; Xu G; Anderson J; Wong M; Jankowsky J; Holtz G; Gonzalez V; Wong PC; Price DL; Tang F; Wagner S; Borchelt DR. 2001. Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice. Hum Mol Genet 10(22):2525-37. [PubMed: 11709540] [MGI Ref ID J:72987]
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Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, The Jackson Laboratory will maintain this line by mating (APP695/0, +/+) females with (+/+, PSEN1/0) males (or reciprocal). The transgenes are not linked (only 1 in 4 pups is a double transgenic); and the integration site is unknown. The Jackson Laboratory will distribute mice with the following genotypes: (PARENT 1) hemizygous APP695, wildtype PSEN1; (PARENT 2) wildtype APP695, hemizygous PSEN1; and (OFFSPRING) double hemizygotes. Control mice can be generated from this breeding pair or investigators can consider C57BL/6J (Stock 000664). While the donating investigator warns that transgenic females can exhibit suboptimal mothering of litters, no such complications have been observed in our colonies to date at The Jackson Laboratory (Jun 2006). Homozygosity may result in sterile males and reduced viability of females, and should be avoided for breeding stocks. Mating System See above Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $239.00 Female or Male Hemizygous for Tg(APP695)3Dbo, Hemizygous for Tg(PSEN1dE9)S9Dbo $239.00 Female or Male Hemizygous for Tg(APP695)3Dbo, Noncarrier Individual Mouse $239.00 Female or Male Noncarrier, Hemizygous for Tg(PSEN1dE9)S9Dbo
Pairs /Price (US dollars $) Pair Genotype $478.00 Noncarrier, Hemizygous for Tg(PSEN1dE9)S9Dbo x Hemizygous for Tg(APP695)3Dbo, Noncarrier
Additional Supply Details
| Pricing for International shipping destinations |
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Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $310.70 Female or Male Hemizygous for Tg(APP695)3Dbo, Hemizygous for Tg(PSEN1dE9)S9Dbo $310.70 Female or Male Hemizygous for Tg(APP695)3Dbo, Noncarrier Individual Mouse $310.70 Female or Male Noncarrier, Hemizygous for Tg(PSEN1dE9)S9Dbo
Pairs /Price (US dollars $) Pair Genotype $621.40 Noncarrier, Hemizygous for Tg(PSEN1dE9)S9Dbo x Hemizygous for Tg(APP695)3Dbo, Noncarrier
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 | ||
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| Noncarrier | ||
| 000664 C57BL/6J | ||
| 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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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
See Terms of Use tab for General Terms and Conditions
The Jackson Laboratory's Genotype Promise
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering and Purchasing Information
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Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
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For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.
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In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. In purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.