Strain Name:

B6.129-Psen1tm1Mpm/J

Stock Number:

004193

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Availability:

Cryopreserved - Ready for recovery

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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

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator George M Martin,   University of Washington

Description
The targeted allele (PS1M146VKI) causes a mutation of the mouse Psen1 gene that results in expression of a presenilin-1 protein with the human familial Alzheimer's disease-linked mutation PS1M146V. The neo cassette was deleted from the targeted allele (using a CMV-Cre transgenic line of mice). Published findings indicate that this alteration should not influence the level of expression of mutant PS1. Northern blot analysis and RT-PCR determined mRNA expression of the targeted mutant allele is normal. Homozygous PS1M146VKI mice produce only the mutant gene product. Mice that express this targeted allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Neurodegeneration seen in wild-type mice caused by excitotoxin kainate treatment is increased and accelerated in this mutant strain. Cultured cells expressing the mutant protein exhibit perturbed neuronal calcium homeostasis. This mutant mouse strain represents a model that may be useful in studies of familial Alzheimer's disease in humans.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was utilized in constructing this mutant. A mutagenized DNA sequence of exon 5 of the mouse Psen1 gene was targeted for the Psen1 allele. The construct was electroporated into 129X1/SvJ x 129S1/Sv-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric male animals were bred to C57BL/6 females to produce mice heterozygous for the mutation. These mice were then bred to a CMV-cre transgenic strain to delete the neo cassette from the targeted allele.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

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View Alzheimer's Disease Models     (109 strains)

Strains carrying   Psen1tm1Mpm allele
004807   B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax
View Strains carrying   Psen1tm1Mpm     (1 strain)

Strains carrying other alleles of Psen1
003615   B6.129-Psen1tm1Shn/J
007685   B6.129P2-Psen1tm1Vln/J
004825   B6.129S4-Psen1tm2Shn/J
007605   B6;129P-Psen1tm1Vln/J
003822   B6;129S-Psen1tm1Shn/J
024025   B6N(Cg)-Psen1tm1.1(KOMP)Vlcg/J
View Strains carrying other alleles of Psen1     (6 strains)

Additional Web Information

JAX® NOTES, Summer 2004; 494. New Mouse Models for Alzheimer's Disease Research.
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

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Alzheimer Disease 3
- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).
Alzheimer Disease; AD
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Acne Inversa, Familial, 3; ACNINV3   (PSEN1)
Cardiomyopathy, Dilated, 1u; CMD1U   (PSEN1)
Frontotemporal Dementia; FTD   (PSEN1)
Pick Disease of Brain   (PSEN1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Psen1tm1Mpm/Psen1tm1Mpm

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6
  • nervous system phenotype
  • increased susceptibility to neuronal excitotoxicity
    • kainate-induced degeneration and death of CA3, CA1, and hilar neurons is accelerated and increased in mutants compared to wild-type   (MGI Ref ID J:51950)
    • cultured hippocampal neurons show increased susceptibility to death induced by glutamate, due to impaired calcium homeostasis, increased oxidative stress, and mitochondrial dysfunction   (MGI Ref ID J:51950)
  • neurodegeneration
    • homozygotes are hypersensitive to seizure-induced synaptic degeneration and necrotic neuronal death in the hippocampus   (MGI Ref ID J:51950)
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • homozygotes do not exhibit a deficit in contextual fear learning at 3 months of age   (MGI Ref ID J:91277)
    • homozygous mice do not differ in performance in Morris water maze or in contextual fear conditioning   (MGI Ref ID J:99604)
  • homeostasis/metabolism phenotype
  • increased susceptibility to neuronal excitotoxicity
    • kainate-induced degeneration and death of CA3, CA1, and hilar neurons is accelerated and increased in mutants compared to wild-type   (MGI Ref ID J:51950)
    • cultured hippocampal neurons show increased susceptibility to death induced by glutamate, due to impaired calcium homeostasis, increased oxidative stress, and mitochondrial dysfunction   (MGI Ref ID J:51950)
  • cellular phenotype
  • increased susceptibility to neuronal excitotoxicity
    • kainate-induced degeneration and death of CA3, CA1, and hilar neurons is accelerated and increased in mutants compared to wild-type   (MGI Ref ID J:51950)
    • cultured hippocampal neurons show increased susceptibility to death induced by glutamate, due to impaired calcium homeostasis, increased oxidative stress, and mitochondrial dysfunction   (MGI Ref ID J:51950)
View Research Applications

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

Neurobiology Research
Alzheimer's Disease
      Presenilin mutants

Psen1tm1Mpm related

Developmental Biology Research
Neurodevelopmental Defects
Postnatal Lethality
      Homozygous
Skeletal Defects

Neurobiology Research
Alzheimer's Disease
Behavioral and Learning Defects
Neurodegeneration
Neurodevelopmental Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Psen1tm1Mpm
Allele Name targeted mutation 1, Mark P Mattson
Allele Type Targeted
Common Name(s) PS-1 M146V KI; PS1KI; PS1M146V; PS1M146VKI-;
Mutation Made By George Martin,   University of Washington
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Promoter Psen1, presenilin 1, mouse, laboratory
Molecular Note Point mutations were introduced into the coding region of exon 5 that altered the codons corresponding to amino acids 145 and 146 from isoleucine and methionine to valine and valine, respectively. A lox-P flanked neomycin cassette was also introduced into exon 4. F2 mice exhibited the expected polymorphism of the targeted allele when genomic DNA was amplified with exon 5 specific primers and the products were digested with the appropriate restriction enzyme. Northern blot analysis of total brain RNA using a Psen1 specific antibody showed that the targeted allele was expressed at normal physiological levels in homozygous mutant mice. [MGI Ref ID J:51950]

Genotyping

Genotyping Information

Genotyping Protocols

Psen1tm1Mpm, Pyrosequencing
Psen1tm1Mpm-EP, End Point Analysis
Psen1tm1Mpm, Restriction Enzyme Digest


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Guo Q; Fu W; Sopher BL; Miller MW; Ware CB; Martin GM; Mattson MP. 1999. Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice. Nat Med 5(1):101-6. [PubMed: 9883847]  [MGI Ref ID J:51950]

Additional References

Chan SL; Mayne M; Holden CP; Geiger JD; Mattson MP. 2000. Presenilin-1 mutations increase levels of ryanodine receptors and calcium release in PC12 cells and cortical neurons. J Biol Chem 275(24):18195-200. [PubMed: 10764737]  [MGI Ref ID J:62820]

Guo Q; Sebastian L; Sopher BL; Miller MW; Glazner GW; Ware CB; Martin GM; Mattson MP. 1999. Neurotrophic factors [activity-dependent neurotrophic factor (ADNF) and basic fibroblast growth factor (bFGF)] interrupt excitotoxic neurodegenerative cascades promoted by a PS1 mutation. Proc Natl Acad Sci U S A 96(7):4125-30. [PubMed: 10097174]  [MGI Ref ID J:54086]

Leissring MA; Akbari Y; Fanger CM; Cahalan MD; Mattson MP; LaFerla FM. 2000. Capacitative calcium entry deficits and elevated luminal calcium content in mutant presenilin-1 knockin mice. J Cell Biol 149(4):793-8. [PubMed: 10811821]  [MGI Ref ID J:62231]

Oddo S; Caccamo A; Shepherd JD; Murphy MP; Golde TE; Kayed R; Metherate R; Mattson MP; Akbari Y; LaFerla FM. 2003. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 39(3):409-21. [PubMed: 12895417]  [MGI Ref ID J:84847]

Zhu H; Guo Q; Mattson MP. 1999. Dietary restriction protects hippocampal neurons against the death-promoting action of a presenilin-1 mutation. Brain Res 842(1):224-9. [PubMed: 10526115]  [MGI Ref ID J:57847]

Psen1tm1Mpm related

Adebakin A; Bradley J; Gumusgoz S; Waters EJ; Lawrence CB. 2012. Impaired satiation and increased feeding behaviour in the triple-transgenic Alzheimer's disease mouse model. PLoS One 7(10):e45179. [PubMed: 23056194]  [MGI Ref ID J:192107]

Algarzae N; Hebron M; Miessau M; Moussa CE. 2012. Parkin prevents cortical atrophy and Abeta-induced alterations of brain metabolism: (1)(3)C NMR and magnetic resonance imaging studies in AD models. Neuroscience 225:22-34. [PubMed: 22960314]  [MGI Ref ID J:192478]

Alvarado-Martinez R; Salgado-Puga K; Pena-Ortega F. 2013. Amyloid beta inhibits olfactory bulb activity and the ability to smell. PLoS One 8(9):e75745. [PubMed: 24086624]  [MGI Ref ID J:206016]

Arsenault D; Dal-Pan A; Tremblay C; Bennett DA; Guitton MJ; De Koninck Y; Tonegawa S; Calon F. 2013. PAK inactivation impairs social recognition in 3xTg-AD Mice without increasing brain deposition of tau and Abeta. J Neurosci 33(26):10729-40. [PubMed: 23804095]  [MGI Ref ID J:199637]

Arsenault D; Julien C; Tremblay C; Calon F. 2011. DHA improves cognition and prevents dysfunction of entorhinal cortex neurons in 3xTg-AD mice. PLoS One 6(2):e17397. [PubMed: 21383850]  [MGI Ref ID J:171054]

Attar A; Liu T; Chan WT; Hayes J; Nejad M; Lei K; Bitan G. 2013. A shortened Barnes maze protocol reveals memory deficits at 4-months of age in the triple-transgenic mouse model of Alzheimer's disease. PLoS One 8(11):e80355. [PubMed: 24236177]  [MGI Ref ID J:209208]

Badiola N; Alcalde V; Pujol A; Munter LM; Multhaup G; Lleo A; Coma M; Soler-Lopez M; Aloy P. 2013. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One 8(3):e58837. [PubMed: 23520537]  [MGI Ref ID J:200185]

Baeta-Corral R; Gimenez-Llort L. 2014. Bizarre behaviors and risk assessment in 3xTg-AD mice at early stages of the disease. Behav Brain Res 258:97-105. [PubMed: 24144550]  [MGI Ref ID J:207948]

Baglietto-Vargas D; Kitazawa M; Le EJ; Estrada-Hernandez T; Rodriguez-Ortiz CJ; Medeiros R; Green KN; LaFerla FM. 2014. Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition. Neurobiol Dis 62:407-15. [PubMed: 24176788]  [MGI Ref ID J:207203]

Banaceur S; Banasr S; Sakly M; Abdelmelek H. 2013. Whole body exposure to 2.4 GHz WIFI signals: effects on cognitive impairment in adult triple transgenic mouse models of Alzheimer's disease (3xTg-AD). Behav Brain Res 240:197-201. [PubMed: 23195115]  [MGI Ref ID J:197070]

Barak B; Shvarts-Serebro I; Modai S; Gilam A; Okun E; Michaelson DM; Mattson MP; Shomron N; Ashery U. 2013. Opposing actions of environmental enrichment and Alzheimer's disease on the expression of hippocampal microRNAs in mouse models. Transl Psychiatry 3:e304. [PubMed: 24022509]  [MGI Ref ID J:202026]

Barron AM; Rosario ER; Elteriefi R; Pike CJ. 2013. Sex-specific effects of high fat diet on indices of metabolic syndrome in 3xTg-AD mice: implications for Alzheimer's disease. PLoS One 8(10):e78554. [PubMed: 24205258]  [MGI Ref ID J:209228]

Billings LM; Oddo S; Green KN; McGaugh JL; Laferla FM. 2005. Intraneuronal Abeta causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice. Neuron 45(5):675-88. [PubMed: 15748844]  [MGI Ref ID J:99604]

Bittner T; Fuhrmann M; Burgold S; Ochs SM; Hoffmann N; Mitteregger G; Kretzschmar H; LaFerla FM; Herms J. 2010. Multiple events lead to dendritic spine loss in triple transgenic Alzheimer's disease mice. PLoS One 5(11):e15477. [PubMed: 21103384]  [MGI Ref ID J:166981]

Blaney CE; Gunn RK; Stover KR; Brown RE. 2013. Maternal genotype influences behavioral development of 3xTg-AD mouse pups. Behav Brain Res 252C:40-48. [PubMed: 23711927]  [MGI Ref ID J:199110]

Blurton-Jones M; Kitazawa M; Martinez-Coria H; Castello NA; Muller FJ; Loring JF; Yamasaki TR; Poon WW; Green KN; LaFerla FM. 2009. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci U S A 106(32):13594-9. [PubMed: 19633196]  [MGI Ref ID J:152002]

Boeras DI; Granic A; Padmanabhan J; Crespo NC; Rojiani AM; Potter H. 2008. Alzheimer's presenilin 1 causes chromosome missegregation and aneuploidy. Neurobiol Aging 29(3):319-28. [PubMed: 17169464]  [MGI Ref ID J:135054]

Bories C; Guitton MJ; Julien C; Tremblay C; Vandal M; Msaid M; De Koninck Y; Calon F. 2012. Sex-dependent alterations in social behaviour and cortical synaptic activity coincide at different ages in a model of Alzheimer's disease. PLoS One 7(9):e46111. [PubMed: 23029404]  [MGI Ref ID J:191965]

Born HA; Kim JY; Savjani RR; Das P; Dabaghian YA; Guo Q; Yoo JW; Schuler DR; Cirrito JR; Zheng H; Golde TE; Noebels JL; Jankowsky JL. 2014. Genetic suppression of transgenic APP rescues Hypersynchronous network activity in a mouse model of Alzeimer's disease. J Neurosci 34(11):3826-40. [PubMed: 24623762]  [MGI Ref ID J:209607]

Bryleva EY; Rogers MA; Chang CC; Buen F; Harris BT; Rousselet E; Seidah NG; Oddo S; LaFerla FM; Spencer TA; Hickey WF; Chang TY. 2010. ACAT1 gene ablation increases 24(S)-hydroxycholesterol content in the brain and ameliorates amyloid pathology in mice with AD. Proc Natl Acad Sci U S A 107(7):3081-6. [PubMed: 20133765]  [MGI Ref ID J:157545]

Caccamo A; Maldonado MA; Bokov AF; Majumder S; Oddo S. 2010. CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 107(52):22687-92. [PubMed: 21149712]  [MGI Ref ID J:167287]

Caccamo A; Maldonado MA; Majumder S; Medina DX; Holbein W; Magri A; Oddo S. 2011. Naturally Secreted Amyloid-{beta} Increases Mammalian Target of Rapamycin (mTOR) Activity via a PRAS40-mediated Mechanism. J Biol Chem 286(11):8924-32. [PubMed: 21266573]  [MGI Ref ID J:170949]

Caccamo A; Oddo S; Billings LM; Green KN; Martinez-Coria H; Fisher A; LaFerla FM. 2006. M1 receptors play a central role in modulating AD-like pathology in transgenic mice. Neuron 49(5):671-82. [PubMed: 16504943]  [MGI Ref ID J:107582]

Carvalho C; Cardoso S; Correia SC; Santos RX; Santos MS; Baldeiras I; Oliveira CR; Moreira PI. 2012. Metabolic alterations induced by sucrose intake and Alzheimer's disease promote similar brain mitochondrial abnormalities. Diabetes 61(5):1234-42. [PubMed: 22427376]  [MGI Ref ID J:196853]

Cassano T; Romano A; Macheda T; Colangeli R; Cimmino CS; Petrella A; Laferla FM; Cuomo V; Gaetani S. 2011. Olfactory memory is impaired in a triple transgenic model of Alzheimer disease. Behav Brain Res 224(2):408-12. [PubMed: 21741995]  [MGI Ref ID J:175693]

Cassano T; Serviddio G; Gaetani S; Romano A; Dipasquale P; Cianci S; Bellanti F; Laconca L; Romano AD; Padalino I; LaFerla FM; Nicoletti F; Cuomo V; Vendemiale G. 2012. Glutamatergic alterations and mitochondrial impairment in a murine model of Alzheimer disease. Neurobiol Aging 33(6):1121.e1-12. [PubMed: 22035587]  [MGI Ref ID J:188184]

Castello NA; Green KN; LaFerla FM. 2012. Genetic knockdown of brain-derived neurotrophic factor in 3xTg-AD mice does not alter Abeta or tau pathology. PLoS One 7(8):e39566. [PubMed: 22870188]  [MGI Ref ID J:189666]

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Oddo S; Caccamo A; Smith IF; Green KN; Laferla FM. 2006. A Dynamic Relationship between Intracellular and Extracellular Pools of A{beta}. Am J Pathol 168(1):184-94. [PubMed: 16400022]  [MGI Ref ID J:104358]

Oddo S; Caccamo A; Tran L; Lambert MP; Glabe CG; Klein WL; LaFerla FM. 2006. Temporal profile of amyloid-beta (Abeta) oligomerization in an in vivo model of Alzheimer disease. A link between Abeta and tau pathology. J Biol Chem 281(3):1599-604. [PubMed: 16282321]  [MGI Ref ID J:107286]

Oddo S; Caccamo A; Tseng B; Cheng D; Vasilevko V; Cribbs DH; LaFerla FM. 2008. Blocking Abeta42 accumulation delays the onset and progression of tau pathology via the C terminus of heat shock protein70-interacting protein: a mechanistic link between Abeta and tau pathology. J Neurosci 28(47):12163-75. [PubMed: 19020010]  [MGI Ref ID J:142370]

Odero GL; Oikawa K; Glazner KA; Schapansky J; Grossman D; Thiessen JD; Motnenko A; Ge N; Martin M; Glazner GW; Albensi BC. 2010. Evidence for the involvement of calbindin D28k in the presenilin 1 model of Alzheimer's disease. Neuroscience 169(1):532-43. [PubMed: 20399254]  [MGI Ref ID J:165240]

Olabarria M; Noristani HN; Verkhratsky A; Rodriguez JJ. 2010. Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer's disease. Glia 58(7):831-8. [PubMed: 20140958]  [MGI Ref ID J:168053]

Orr ME; Salinas A; Buffenstein R; Oddo S. 2014. Mammalian target of rapamycin hyperactivity mediates the detrimental effects of a high sucrose diet on Alzheimer's disease pathology. Neurobiol Aging 35(6):1233-42. [PubMed: 24411482]  [MGI Ref ID J:213887]

Overk CR; Lu PY; Wang YT; Choi J; Shaw JW; Thatcher GR; Mufson EJ. 2012. Effects of aromatase inhibition versus gonadectomy on hippocampal complex amyloid pathology in triple transgenic mice. Neurobiol Dis 45(1):479-87. [PubMed: 21945538]  [MGI Ref ID J:180010]

Payette DJ; Xie J; Guo Q. 2007. Reduction in CHT1-mediated choline uptake in primary neurons from presenilin-1 M146V mutant knock-in mice. Brain Res 1135(1):12-21. [PubMed: 17196556]  [MGI Ref ID J:118185]

Peng J; Liang G; Inan S; Wu Z; Joseph DJ; Meng Q; Peng Y; Eckenhoff MF; Wei H. 2012. Dantrolene ameliorates cognitive decline and neuropathology in Alzheimer triple transgenic mice. Neurosci Lett 516(2):274-9. [PubMed: 22516463]  [MGI Ref ID J:188750]

Perez SE; He B; Muhammad N; Oh KJ; Fahnestock M; Ikonomovic MD; Mufson EJ. 2011. Cholinotrophic basal forebrain system alterations in 3xTg-AD transgenic mice. Neurobiol Dis 41(2):338-52. [PubMed: 20937383]  [MGI Ref ID J:168651]

Pietri M; Dakowski C; Hannaoui S; Alleaume-Butaux A; Hernandez-Rapp J; Ragagnin A; Mouillet-Richard S; Haik S; Bailly Y; Peyrin JM; Launay JM; Kellermann O; Schneider B. 2013. PDK1 decreases TACE-mediated alpha-secretase activity and promotes disease progression in prion and Alzheimer's diseases. Nat Med 19(9):1124-31. [PubMed: 23955714]  [MGI Ref ID J:202038]

Pietropaolo S; Sun Y; Li R; Brana C; Feldon J; Yee BK. 2008. The impact of voluntary exercise on mental health in rodents: A neuroplasticity perspective. Behav Brain Res 192(1):42-60. [PubMed: 18468702]  [MGI Ref ID J:136980]

Pratt KG; Zimmerman EC; Cook DG; Sullivan JM. 2011. Presenilin 1 regulates homeostatic synaptic scaling through Akt signaling. Nat Neurosci 14(9):1112-4. [PubMed: 21841774]  [MGI Ref ID J:179786]

Rabinovich-Nikitin I; Rakover IS; Becker M; Solomon B. 2012. Beneficial effect of antibodies against beta- secretase cleavage site of APP on Alzheimer's-like pathology in triple-transgenic mice. PLoS One 7(10):e46650. [PubMed: 23071606]  [MGI Ref ID J:192092]

Resende R; Moreira PI; Proenca T; Deshpande A; Busciglio J; Pereira C; Oliveira CR. 2008. Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease. Free Radic Biol Med 44(12):2051-7. [PubMed: 18423383]  [MGI Ref ID J:136275]

Ribe EM; Serrano-Saiz E; Akpan N; Troy CM. 2008. Mechanisms of neuronal death in disease: defining the models and the players. Biochem J 415(2):165-82. [PubMed: 18800967]  [MGI Ref ID J:141307]

Rice RA; Berchtold NC; Cotman CW; Green KN. 2014. Age-related downregulation of the CaV3.1 T-type calcium channel as a mediator of amyloid beta production. Neurobiol Aging 35(5):1002-11. [PubMed: 24268883]  [MGI Ref ID J:212737]

Rodriguez JJ; Jones VC; Tabuchi M; Allan SM; Knight EM; LaFerla FM; Oddo S; Verkhratsky A. 2008. Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer's disease. PLoS ONE 3(8):e2935. [PubMed: 18698410]  [MGI Ref ID J:140591]

Rodriguez JJ; Noristani HN; Hilditch T; Olabarria M; Yeh CY; Witton J; Verkhratsky A. 2013. Increased densities of resting and activated microglia in the dentate gyrus follow senile plaque formation in the CA1 subfield of the hippocampus in the triple transgenic model of Alzheimer's disease. Neurosci Lett 552:129-34. [PubMed: 23827221]  [MGI Ref ID J:201677]

Romberg C; Mattson MP; Mughal MR; Bussey TJ; Saksida LM. 2011. Impaired attention in the 3xTgAD mouse model of Alzheimer's disease: rescue by donepezil (Aricept). J Neurosci 31(9):3500-7. [PubMed: 21368062]  [MGI Ref ID J:170670]

Rosario ER; Carroll J; Pike CJ. 2010. Testosterone regulation of Alzheimer-like neuropathology in male 3xTg-AD mice involves both estrogen and androgen pathways. Brain Res 1359:281-90. [PubMed: 20807511]  [MGI Ref ID J:166622]

Rosario ER; Carroll JC; Pike CJ. 2012. Evaluation of the effects of testosterone and luteinizing hormone on regulation of beta-amyloid in male 3xTg-AD mice. Brain Res 1466:137-45. [PubMed: 22587890]  [MGI Ref ID J:186440]

Rothman SM; Herdener N; Camandola S; Texel SJ; Mughal MR; Cong WN; Martin B; Mattson MP. 2012. 3xTgAD mice exhibit altered behavior and elevated Abeta after chronic mild social stress. Neurobiol Aging 33(4):830.e1-12. [PubMed: 21855175]  [MGI Ref ID J:188192]

Saito T; Suemoto T; Brouwers N; Sleegers K; Funamoto S; Mihira N; Matsuba Y; Yamada K; Nilsson P; Takano J; Nishimura M; Iwata N; Van Broeckhoven C; Ihara Y; Saido TC. 2011. Potent amyloidogenicity and pathogenicity of Abeta43. Nat Neurosci 14(8):1023-32. [PubMed: 21725313]  [MGI Ref ID J:175901]

Sancheti H; Akopian G; Yin F; Brinton RD; Walsh JP; Cadenas E. 2013. Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer's disease. PLoS One 8(7):e69830. [PubMed: 23875003]  [MGI Ref ID J:204388]

Sensi SL; Rapposelli IG; Frazzini V; Mascetra N. 2008. Altered oxidant-mediated intraneuronal zinc mobilization in a triple transgenic mouse model of Alzheimer's disease. Exp Gerontol 43(5):488-492. [PubMed: 18068923]  [MGI Ref ID J:135291]

Shilling D; Muller M; Takano H; Mak DO; Abel T; Coulter DA; Foskett JK. 2014. Suppression of InsP3 receptor-mediated Ca2+ signaling alleviates mutant presenilin-linked familial Alzheimer's disease pathogenesis. J Neurosci 34(20):6910-23. [PubMed: 24828645]  [MGI Ref ID J:211264]

Singh C; Liu L; Wang JM; Irwin RW; Yao J; Chen S; Henry S; Thompson RF; Brinton RD. 2012. Allopregnanolone restores hippocampal-dependent learning and memory and neural progenitor survival in aging 3xTgAD and nonTg mice. Neurobiol Aging 33(8):1493-506. [PubMed: 21803451]  [MGI Ref ID J:188197]

Smith IF; Hitt B; Green KN; Oddo S; LaFerla FM. 2005. Enhanced caffeine-induced Ca2+ release in the 3xTg-AD mouse model of Alzheimer's disease. J Neurochem 94(6):1711-8. [PubMed: 16156741]  [MGI Ref ID J:101318]

Song JM; DiBattista AM; Sung YM; Ahn JM; Turner RS; Yang J; Pak DT; Lee HK; Hoe HS. 2014. A tetra(ethylene glycol) derivative of benzothiazole aniline ameliorates dendritic spine density and cognitive function in a mouse model of Alzheimer's disease. Exp Neurol 252:105-13. [PubMed: 24316432]  [MGI Ref ID J:210695]

Sterniczuk R; Antle MC; Laferla FM; Dyck RH. 2010. Characterization of the 3xTg-AD mouse model of Alzheimer's disease: part 2. Behavioral and cognitive changes. Brain Res 1348:149-55. [PubMed: 20558146]  [MGI Ref ID J:163336]

Sterniczuk R; Dyck RH; Laferla FM; Antle MC. 2010. Characterization of the 3xTg-AD mouse model of Alzheimer's disease: part 1. Circadian changes. Brain Res 1348:139-48. [PubMed: 20471965]  [MGI Ref ID J:163362]

Stutzmann GE; Caccamo A; LaFerla FM; Parker I. 2004. Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer's-linked mutation in presenilin1 results in exaggerated Ca2+ signals and altered membrane excitability. J Neurosci 24(2):508-13. [PubMed: 14724250]  [MGI Ref ID J:87452]

Stutzmann GE; Smith I; Caccamo A; Oddo S; Laferla FM; Parker I. 2006. Enhanced ryanodine receptor recruitment contributes to Ca2+ disruptions in young, adult, and aged Alzheimer's disease mice. J Neurosci 26(19):5180-9. [PubMed: 16687509]  [MGI Ref ID J:108684]

Sun S; Zhang H; Liu J; Popugaeva E; Xu NJ; Feske S; White CL 3rd; Bezprozvanny I. 2014. Reduced synaptic STIM2 expression and impaired store-operated calcium entry cause destabilization of mature spines in mutant presenilin mice. Neuron 82(1):79-93. [PubMed: 24698269]  [MGI Ref ID J:213159]

Sy M; Kitazawa M; Medeiros R; Whitman L; Cheng D; Lane TE; Laferla FM. 2011. Inflammation induced by infection potentiates tau pathological features in transgenic mice. Am J Pathol 178(6):2811-22. [PubMed: 21531375]  [MGI Ref ID J:173178]

Takahashi RH; Capetillo-Zarate E; Lin MT; Milner TA; Gouras GK. 2010. Co-occurrence of Alzheimer's disease beta-amyloid and tau pathologies at synapses. Neurobiol Aging 31(7):1145-52. [PubMed: 18771816]  [MGI Ref ID J:161990]

Takata K; Kitamura Y; Nakata Y; Matsuoka Y; Tomimoto H; Taniguchi T; Shimohama S. 2009. Involvement of WAVE accumulation in Abeta/APP pathology-dependent tangle modification in Alzheimer's disease. Am J Pathol 175(1):17-24. [PubMed: 19497998]  [MGI Ref ID J:150061]

Torres-Lista V; Gimenez-Llort L. 2013. Impairment of nesting behaviour in 3xTg-AD mice. Behav Brain Res 247:153-7. [PubMed: 23523959]  [MGI Ref ID J:197629]

Tseng BP; Green KN; Chan JL; Blurton-Jones M; LaFerla FM. 2008. Abeta inhibits the proteasome and enhances amyloid and tau accumulation. Neurobiol Aging 29(11):1607-18. [PubMed: 17544172]  [MGI Ref ID J:140906]

Um JW; Kaufman AC; Kostylev M; Heiss JK; Stagi M; Takahashi H; Kerrisk ME; Vortmeyer A; Wisniewski T; Koleske AJ; Gunther EC; Nygaard HB; Strittmatter SM. 2013. Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer abeta oligomer bound to cellular prion protein. Neuron 79(5):887-902. [PubMed: 24012003]  [MGI Ref ID J:201741]

Walls KC; Ager RR; Vasilevko V; Cheng D; Medeiros R; LaFerla FM. 2014. p-Tau immunotherapy reduces soluble and insoluble tau in aged 3xTg-AD mice. Neurosci Lett 575:96-100. [PubMed: 24887583]  [MGI Ref ID J:214748]

Wang G; Silva J; Dasgupta S; Bieberich E. 2008. Long-chain ceramide is elevated in presenilin 1 (PS1M146V) mouse brain and induces apoptosis in PS1 astrocytes. Glia 56(4):449-56. [PubMed: 18205190]  [MGI Ref ID J:156283]

Wang JM; Singh C; Liu L; Irwin RW; Chen S; Chung EJ; Thompson RF; Brinton RD. 2010. Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 107(14):6498-503. [PubMed: 20231471]  [MGI Ref ID J:159326]

Wang R; Dineley KT; Sweatt JD; Zheng H. 2004. Presenilin 1 familial Alzheimer's disease mutation leads to defective associative learning and impaired adult neurogenesis. Neuroscience 126(2):305-12. [PubMed: 15207348]  [MGI Ref ID J:91277]

Wang R; Wang B; He W; Zheng H. 2006. Wild-type presenilin 1 protects against Alzheimer disease mutation-induced amyloid pathology. J Biol Chem 281(22):15330-6. [PubMed: 16574645]  [MGI Ref ID J:113453]

Wang Y; Greig NH; Yu QS; Mattson MP. 2009. Presenilin-1 mutation impairs cholinergic modulation of synaptic plasticity and suppresses NMDA currents in hippocampus slices. Neurobiol Aging 30(7):1061-8. [PubMed: 18068871]  [MGI Ref ID J:152964]

Wang Y; Mattson MP. 2014. L-type Ca2+ currents at CA1 synapses, but not CA3 or dentate granule neuron synapses, are increased in 3xTgAD mice in an age-dependent manner. Neurobiol Aging 35(1):88-95. [PubMed: 23932880]  [MGI Ref ID J:211983]

Winton MJ; Lee EB; Sun E; Wong MM; Leight S; Zhang B; Trojanowski JQ; Lee VM. 2011. Intraneuronal APP, Not Free A{beta} Peptides in 3xTg-AD Mice: Implications for Tau versus A{beta}-Mediated Alzheimer Neurodegeneration. J Neurosci 31(21):7691-9. [PubMed: 21613482]  [MGI Ref ID J:173328]

Xie J; Chang X; Zhang X; Guo Q. 2001. Aberrant induction of Par-4 is involved in apoptosis of hippocampal neurons in presenilin-1 M146V mutant knock-in mice. Brain Res 915(1):1-10. [PubMed: 11578614]  [MGI Ref ID J:72044]

Yao J; Irwin R; Chen S; Hamilton R; Cadenas E; Brinton RD. 2012. Ovarian hormone loss induces bioenergetic deficits and mitochondrial beta-amyloid. Neurobiol Aging 33(8):1507-21. [PubMed: 21514693]  [MGI Ref ID J:188212]

Yao J; Irwin RW; Zhao L; Nilsen J; Hamilton RT; Brinton RD. 2009. Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 106(34):14670-5. [PubMed: 19667196]  [MGI Ref ID J:151942]

Ye H; Jalini S; Mylvaganam S; Carlen P. 2010. Activation of large-conductance Ca(2+)-activated K(+) channels depresses basal synaptic transmission in the hippocampal CA1 area in APP (swe/ind) TgCRND8 mice. Neurobiol Aging 31(4):591-604. [PubMed: 18547679]  [MGI Ref ID J:159592]

Zhang Y; Kurup P; Xu J; Carty N; Fernandez SM; Nygaard HB; Pittenger C; Greengard P; Strittmatter SM; Nairn AC; Lombroso PJ. 2010. Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer's disease mouse model. Proc Natl Acad Sci U S A 107(44):19014-9. [PubMed: 20956308]  [MGI Ref ID J:166233]

Zhu H; Guo Q; Mattson MP. 1999. Dietary restriction protects hippocampal neurons against the death-promoting action of a presenilin-1 mutation. Brain Res 842(1):224-9. [PubMed: 10526115]  [MGI Ref ID J:57847]

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

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryThis strain originated on a B6;129 background, and has been backcrossed to C57BL/6 for at least 7 generations (11/01).

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
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.

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. 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. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 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).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
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.

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. 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. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 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).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  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.
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JAX® Mice
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Terms of Use


General Terms and Conditions


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General inquiries regarding Terms of Use

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phone:207-288-6470

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. Unless prohibited by law, 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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