Strain Name:

B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J

Stock Number:

003378

Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6C3F1-TgN(Prn-APP695)3Dbo TgN(Prn-PSEN1)5Dbo    (Changed: 15-DEC-04 )
Type Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Mating SystemSee Colony Maintenance
Specieslaboratory mouse
GenerationF2N2+N1p
 
Donating Investigator David Borchelt,   McKnight Brain Inst, Univ of Florida

Description
These transgenic mice express human presenilin 1 (A246E variant) and a chimeric amyloid precursor protein (APPSwe). The mouse prion protein promoter directs expression of both transgenes. Elevated levels of the AB1-42(43) peptide is detected in brain homogenates. By nine months of age, histological examination of brain tissue 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. These mice provide a useful model for studying the underlying mechanism of amyloid deposition, a process implicated in AD.

Development
Mouse pronuclei (B6C3H) were injected with an expression plasmid containing a mouse prion promoter and a cDNA encoding human presenilin 1 bearing the A246E substitution (line N-5). Another subset of mouse pronuclei (B6C3H) were injected with an expression plasmid containing a cDNA encoding a chimeric amyloid beta (A4) precursor protein, also regulated by the mouse prion promoter (line C3-3). The chimeric APP molecule was created by replacing sequences encoding the Abeta domain of the murine sequence with the cognate sequences of the human gene (mutations K595N, M596L). The two transgenic lines were subsequently mated to generate the double transgenic.

Control Information

  Control
   Noncarrier
   100010 B6C3F1/J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Tg(APP695)3Dbo allele
005866   B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/J
003375   C3B6-Tg(APP695)3Dbo/J
View Strains carrying   Tg(APP695)3Dbo     (2 strains)

View Strains carrying other alleles of APP695     (7 strains)

View Strains carrying other alleles of PSEN1     (6 strains)

View Strains carrying other alleles of Prnp     (18 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

View Related Disease (OMIM) Terms

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Tg(APP695)3Dbo/0 Tg(PSEN1)5Dbo/0

        involves: C3H/HeJ * C57BL/6J
  • nervous system phenotype
  • *normal* nervous system phenotype (MGI Ref ID J:100961)
    • no differences in neuron number in cingulate cortex relative to wild-type
    • abnormal neuron morphology (MGI Ref ID J:43788)
      • dystrophic neuritis associated with reactive gliosis in cortex and hippocampus
    • abnormal neuron physiology (MGI Ref ID J:100961)
      • neurons in cingulate cortex display 3-fold elevation in phosphorylated tumor suppressor protein (pRb) and activated caspase-3 relative to wild-type neurons
    • amyloid beta deposits (MGI Ref ID J:43788)
      • amyloid beta deposits found in cortex and hippocampus tissue from 9 and 12 month old mice and increase in number between 10 ans 12 months of age
      • amyloid beta peptides AB1-40 and AB1-42 are codeposited
      • ratio of amyloid beta peptide 40:42 is 1.75:1
      • exhibits a 50% increase in amyloid beta peptide 42
      • immunoreactive amyloid beta deposits are observed in the cingulate cortex in 12 month-old double transgenic mice; deposits are most evident in gray matter of cingulate and enthorhinal cortex, and to lesser extent in non-neuronal layers of the hippocampal formation
    • astrocytosis (MGI Ref ID J:43788)
      • associated with dystropic neuritis in cortex and hippocampus
  • other phenotype
  • amyloid beta deposits (MGI Ref ID J:43788)
    • amyloid beta deposits found in cortex and hippocampus tissue from 9 and 12 month old mice and increase in number between 10 ans 12 months of age
    • amyloid beta peptides AB1-40 and AB1-42 are codeposited
    • ratio of amyloid beta peptide 40:42 is 1.75:1
    • exhibits a 50% increase in amyloid beta peptide 42
    • immunoreactive amyloid beta deposits are observed in the cingulate cortex in 12 month-old double transgenic mice; deposits are most evident in gray matter of cingulate and enthorhinal cortex, and to lesser extent in non-neuronal layers of the hippocampal formation

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Tg(APP695)3Dbo/0 Tg(PSEN1)5Dbo/0

        B6.Cg-Tg(APP695)3Dbo Tg(PSEN1)5Dbo
  • nervous system phenotype
  • amyloid beta deposits (MGI Ref ID J:100956)
    • at 12 and 17 months of age, females have significantly more plaques in the hippocampus compared to males; plaque load increases dramatically with age in mice, particularly in females
  • behavior/neurological phenotype
  • abnormal discrimination learning (MGI Ref ID J:142183)
    • escape latencies across trial blocks in left-right discrimination learning are elevated and decrease little in comparison to decreased escape latencies exhibited in controls
    • required higher trials to reach criterion and committed more errors in comparison to controls
  • abnormal nest building behavior (MGI Ref ID J:142183)
    • poor nest building ability in comparison to controls
  • abnormal touch/ nociception (MGI Ref ID J:142183)
    • increased irritability in response to touch escape test as compared to control
  • behavioral despair (MGI Ref ID J:142183)
    • increased duration of immobility in Porsolt forced swim test
  • impaired passive avoidance behavior (MGI Ref ID J:142183)
    • poor retention latency exhibited in light-dark step through box
  • other phenotype
  • amyloid beta deposits (MGI Ref ID J:100956)
    • at 12 and 17 months of age, females have significantly more plaques in the hippocampus compared to males; plaque load increases dramatically with age in mice, particularly in females
  • touch/vibrissae phenotype
  • abnormal touch/ nociception (MGI Ref ID J:142183)
    • increased irritability in response to touch escape test as compared to control
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Neurobiology Research
Alzheimer's Disease
      APP and PSEN1 mutants
      Presenilin mutants
      strains expressing mutant APP

Tg(APP695)3Dbo related

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(PSEN1)5Dbo
Allele Name transgene insertion 5, David R Borchelt
Allele Type Transgenic (random, expressed)
Common Name(s) Hu PS1-A246E; PS1 A246E; PS1-A246E; PS1/A246E; PS1A246E;
Mutation Made By David Borchelt,   McKnight Brain Inst, Univ of Florida
Expressed Gene PSEN1, presenilin 1, human
Promoter Prnp, prion protein, mouse, laboratory
General Note This line was generated from founder number N-5.

Transgenic mice that are also transgenic for Tg(APP695)3Dboexpress 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 numerousamyloid 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 consists of a mouse prion promoter and a cDNA encoding human presenilin 1 bearing the A246E substitution found in familial Alzheimer's disease (FAD). Transgene expression was verified by Northern and Western blot analysis of brain extracts derived from transgenic animals. [MGI Ref ID J:80882]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(PSEN1), Melt Curve Analysis
Tg(PSEN1), Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

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]

Additional References

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; 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]

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]

Tg(APP695)3Dbo related

Boissonneault 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; 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 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]

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]

Tg(PSEN1)5Dbo related

Boissonneault 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; 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]

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]

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]

Haughey NJ; Nath A; Chan SL; Borchard AC; Rao MS; Mattson MP. 2002. Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer's disease. J Neurochem 83(6):1509-24. [PubMed: 12472904]  [MGI Ref ID J:80820]

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]

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]

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]

Mirnics ZK; Yan C; Portugal C; Kim TW; Saragovi HU; Sisodia SS; Mirnics K; Schor NF. 2005. P75 neurotrophin receptor regulates expression of neural cell adhesion molecule 1. Neurobiol Dis 20(3):969-85. [PubMed: 16006137]  [MGI Ref ID J:104654]

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]

Parent A; Linden DJ; Sisodia SS; Borchelt DR. 1999. Synaptic transmission and hippocampal long-term potentiation in transgenic mice expressing FAD-linked presenilin 1. Neurobiol Dis 6(1):56-62. [PubMed: 10078973]  [MGI Ref ID J:57519]

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]

Salehi A; Delcroix JD; Belichenko PV; Zhan K; Wu C; Valletta JS; Takimoto-Kimura R; Kleschevnikov AM; Sambamurti K; Chung PP; Xia W; Villar A; Campbell WA; Kulnane LS; Nixon RA; Lamb BT; Epstein CJ; Stokin GB; Goldstein LS; Mobley WC. 2006. Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51(1):29-42. [PubMed: 16815330]  [MGI Ref ID J:122937]

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]

Stokin GB; Almenar-Queralt A; Gunawardena S; Rodrigues EM; Falzone T; Kim J; Lillo C; Mount SL; Roberts EA; McGowan E; Williams DS; Goldstein LS. 2008. Amyloid precursor protein-induced axonopathies are independent of amyloid-beta peptides. Hum Mol Genet 17(22):3474-86. [PubMed: 18694898]  [MGI Ref ID J:140396]

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]

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]

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]

Zhou XW; Tanila H; Pei JJ. 2008. Parallel increase in p70 kinase activation and tau phosphorylation (S262) with Abeta overproduction. FEBS Lett 582(2):159-164. [PubMed: 18068129]  [MGI Ref ID J:130326]

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]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryThe strain originated on a mixed B6;C3H background. The investigator maintains the line by mating double transgenics to C3B6F1 mice. The double transgenics are hemizygous; they are not linked (only 1 in 4 pups is a double transgenic); and the integration site is unknown. Reproduction is excellent. TJL maintains this line by mating (APP695/0, +/+) x (+/+, PSEN1/0) (or reciprocal) to distribute mice APP695/+, PSEN1/+. Expected coat colors: agouti, black. TJL will supply 1) hemizygous APP695, wildtype PSEN1; 2) wildtype APP695, hemizygous PSEN1; and 3) double hemizygotes. Breeder pairs will be the hemizygous APP695, wildtype PSEN1 and the wildtype APP695, hemizygous PSEN1 from the colony (and the reciprocal). Control mice can be generated from this breeding pair. Alternatively, investigators can consider B6C3F1/J (Stock 100010).
Mating SystemSee above

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Price (US dollars $)
Cryorecovery Fee $1900.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Price (US dollars $)
Cryorecovery Fee $2470.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Additional Supply Details

Supply Details

Standard SupplyCryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

  • This strain is included in the Induced Mutant Resource Colony collection.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

  Control
   Noncarrier
   100010 B6C3F1/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.

Payment Terms and Conditions

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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Contact Information
Orders & Technical Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.

Contact information

General inquiries

Contracts Administration

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.

No Liability

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.


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