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| These 3xTg-AD mice harbor a Psen1 mutation and the co-injected APPSwe and tauP301L transgenes (Tg(APPSwe,tauP301L)1Lfa)), and may be useful for studying plaque and tangle pathology associated with synaptic dysfunction and Alzheimer's disease. | |||||||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Former Names B6.Cg-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/J (Changed: 07-AUG-09 ) C57BL/6-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/J (Changed: 13-MAR-08 ) C57BL/6-Psen1tm1Mpm Tg(APPSwe, tauP301L)1Lfa/J (Changed: 30-MAR-06 ) Type Mutant Stock; Targeted Mutation; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System See Colony Maintenance Species laboratory mouse Generation F?+ (17-JUL-09) Donating Investigator Frank LaFerla, University of California, Irvine Description
Mice homozygous for all three mutant alleles (3xTg-AD; homozygous for the Psen1 mutation and homozygous for the co-injected APPSwe and tauP301L transgenes (Tg(APPSwe,tauP301L)1Lfa)) are viable, fertile and display no initial gross physical or behavioral abnormalities. Translation of the overexpressed transgenes appears to be restricted to the central nervous system, notably in Alzheimer's disease-relevant areas including the hippocampus and cerebral cortex. A progressive increase in amyloid beta peptide deposition is observed, with intracellular immunoreactivity being detected in some brain regions as early as 3-4 months. Synaptic transmission and long-term potentiation are demonstrably impaired in mice 6 months of age. Between 12-15 months aggregates of conformationally altered and hyperphosphorylated tau are detected in the hippocampus. This mutant mouse exhibits plaque and tangle pathology associated with synaptic dysfunction, traits similar to those observed in Alzheimer's disease patients.Development
Single-cell embryos from mice bearing the presenilin PS1M146V knockin mutation on a mixed C7BL/6;129X1/SvJ;129S1/Sv genetic background (B6;129-Psen1tm1Mpm) were co-injected with two independent mutant human transgenes; amyloid beta precursor protein (APPSwe) and microtubule-associated protein tau (tauP30IL). Both transgenes integrated at the same locus and are under the control of the mouse Thy1.2 regulatory element. Founder mice (line B1) were mated to B6;129-Psen1tm1Mpm mice. Offspring from this cross were bred together, resulting in mice homozygous for all three alleles (3xTg-AD; homozygous for the Psen1 mutation and homozygous for the co-injected APPSwe and tauP301L transgenes (Tg(APPSwe,tauP301L)1Lfa)). Both male and female 3xTg-AD mice on the mixed C7BL/6;129X1/SvJ;129S1/Sv genetic background were sent to The Jackson Laboratory and bred together to establish this colony.
Control Information
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Psen1tm1Mpm allele
004193 B6.129-Psen1tm1Mpm/J View Strains carrying Psen1tm1Mpm (1 strain)
003615 B6.129-Psen1tm1Shn/J 007685 B6.129P2-Psen1tm1Vln/J 007605 B6;129P-Psen1tm1Vln/J 003822 B6;129S-Psen1tm1Shn/J
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
Alzheimer Disease; AD - Models with phenotypic similarity to human disease where etiologies are distinct.2
2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Psen1tm1Mpm/Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/?
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
- nervous system phenotype
- amyloid beta deposits (MGI Ref ID J:107286)
- Abeta oligomers begin to accumulate between 2 and 6 months of age, with continued age-dependent increase observed between 12 and 20 months
- intraneuronal oligomers are detected at 4-6 months of age
- neurofibrillary tangles (MGI Ref ID J:107286)
- tau pathology is detected initially by 6 months of age, and tangle pathology is advanced by 20 months
- other phenotype
- amyloid beta deposits (MGI Ref ID J:107286)
- Abeta oligomers begin to accumulate between 2 and 6 months of age, with continued age-dependent increase observed between 12 and 20 months
- intraneuronal oligomers are detected at 4-6 months of age
Psen1tm1Mpm/Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Tg(APPSwe,tauP301L)1Lfa
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
- behavior/neurological phenotype
- abnormal learning/ memory (MGI Ref ID J:99604)
- in Morris water mazed, learning of task is normal but retention is impaired; 6-month old mice require 6 days of training to achieve escape latency of >20 seconds, compared to 3 days in 2 month old control mice
- at 4 and 6 months, mice show longer escape latencies in the first daily trial relative to the last trial of the previous training day indicating day-to-day retention impairment; 2-month old mice do not show this impairment in retention
- short- (1.5 hr posttraining) and long-term (24 hr posttraining) spatial recognition memory in probe trials are impaired at 6 months, whereas 4-month old mice show similar performance at 1.5 hours and impaired retention at 24 hours
- after clearance of intraneuronal Abeta using antibodies, early retention deficits are ablated, whereas long-term retention remains impaired
- abnormal contextual conditioning behavior (MGI Ref ID J:99604)
- at 6 months, naive and trained mice display significantly impaired long- and short-term retention for contextual fear; at 4 months, mice have normal retention for short-term (1.5 hr) contextual fear but impaired memory of contextual fear at 24 hours
- nervous system phenotype
- amyloid beta deposits (MGI Ref ID J:99604)
- at 6 months, extracellular Abeta plaques are observed in the cerebral cortex, and intracellular accumulation is seen in pyramidal neurons of the CA1 region of hippocampus and within basolateral amygdala and cortical neurons
- prominent intraneuronal Abeta accumulation is present at 4 months, preceding extracellular amyloid plaque formation
- treatment of mice with antibodies to Abeta results in clearance of intraneuroanl Abeta in hippocampus and cortex, but not in amygdala
- other phenotype
- amyloid beta deposits (MGI Ref ID J:99604)
- at 6 months, extracellular Abeta plaques are observed in the cerebral cortex, and intracellular accumulation is seen in pyramidal neurons of the CA1 region of hippocampus and within basolateral amygdala and cortical neurons
- prominent intraneuronal Abeta accumulation is present at 4 months, preceding extracellular amyloid plaque formation
- treatment of mice with antibodies to Abeta results in clearance of intraneuroanl Abeta in hippocampus and cortex, but not in amygdala
This mouse can be used to support research in many areas including:
MAPT relatedMouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease
APP and PSEN1 mutants
Presenilin mutants
strains expressing mutant APP
Behavioral and Learning Defects
Research Tools
Neurobiology Research
Psen1tm1Mpm relatedNeurobiology Research
Parkinson's Disease
Developmental Biology Research
Neurodevelopmental Defects
Postnatal Mortality
Homozygous
Skeletal Defects
Mouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease
Behavioral and Learning Defects
Neurodegeneration
Neurodevelopmental Defects
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Psen1tm1Mpm | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Mark P Mattson | ||
| Allele Type | Targeted (knock-in) | ||
| 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 Name | R1 | ||
| ES Cell Line Strain | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| Gene Symbol and Name | Psen1, presenilin 1 | ||
| Chromosome | 12 | ||
| Gene Common Name(s) | AD3; Ad3h; FAD; PS-1; PS1; S182; alzheimer disease 3 homolog; presenilin-1; | ||
| 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] | ||
| Allele Symbol | Tg(APPSwe,tauP301L)1Lfa | ||
| Allele Name | transgene insertion 1, Frank M LaFerla | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | 3xTg-AD; 3xTgAD; Tg2576/PSEN1; | ||
| Expressed Gene | PSEN1, presenilin 1, human | ||
| Expressed Gene | MAPT, microtubule-associated protein tau, human | ||
| Promoter | Thy1, thymus cell antigen 1, theta, mouse, laboratory | ||
| Molecular Note | To develop a model of Alzheimer's Disease, mice harboring mutant human APP (Swedish double mutation; K670N, M671L) and MAPT (P301L) as well as Psentm1Mpm were generated by microinjection of the APP and MAPT transgenic constructs into single cell embryos harvested from mice homozygous for Psen1tm1Mpm. Southern blot analysis indicated that both transgenic constructs integrated into the same site. Western blot analysis showed APP and MAPT levels to be ~4 fold higher in hemizygous mice and ~6 (APP) to ~7 (Mapt) fold higher homozygous mice, relative to non transgenic mice. Amyloid-Beta peptide (both 40 and 42) was detected in transgenic mice, with greater levels in homozygous mice than in hemizygous mice. Expression was confined to the CNS. Highest steady state levels of proteins were detected in Alzheimer's Disease related regions including the hippocampus and cerebral cortex. Transgenic protein was not detected in the cerebellum. [MGI Ref ID J:84847] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Psen1tm1Mpm, Restriction Enzyme Digest
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
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]
Additional References
Psen1tm1Mpm relatedTg(APPSwe,tauP301L)1Lfa relatedBillings 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]
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]
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]
Chakroborty S; Goussakov I; Miller MB; Stutzmann GE. 2009. Deviant ryanodine receptor-mediated calcium release resets synaptic homeostasis in presymptomatic 3xTg-AD mice. J Neurosci 29(30):9458-70. [PubMed: 19641109] [MGI Ref ID J:151323]
Chan SL; Culmsee C; Haughey N; Klapper W; Mattson MP. 2002. Presenilin-1 mutations sensitize neurons to DNA damage-induced death by a mechanism involving perturbed calcium homeostasis and activation of calpains and caspase-12. Neurobiol Dis 11(1):2-19. [PubMed: 12460542] [MGI Ref ID J:125448]
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]
Clinton LK; Billings LM; Green KN; Caccamo A; Ngo J; Oddo S; McGaugh JL; LaFerla FM. 2007. Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice. Neurobiol Dis 28(1):76-82. [PubMed: 17659878] [MGI Ref ID J:134819]
Fonseca MI; Ager RR; Chu SH; Yazan O; Sanderson SD; LaFerla FM; Taylor SM; Woodruff TM; Tenner AJ. 2009. Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's disease. J Immunol 183(2):1375-83. [PubMed: 19561098] [MGI Ref ID J:151661]
Green KN; Billings LM; Roozendaal B; McGaugh JL; LaFerla FM. 2006. Glucocorticoids increase amyloid-beta and tau pathology in a mouse model of Alzheimer's disease. J Neurosci 26(35):9047-56. [PubMed: 16943563] [MGI Ref ID J:112193]
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]
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]
Guo Q; Sebastian L; Sopher BL; Miller MW; Ware CB; Martin GM ; Mattson MP. 1999. Increased vulnerability of hippocampal neurons from presenilin-1 mutant knock-in mice to amyloid beta-peptide toxicity: central roles of superoxide production and caspase activation. J Neurochem 72(3):1019-29. [PubMed: 10037473] [MGI Ref ID J:53132]
Halagappa VK; Guo Z; Pearson M; Matsuoka Y; Cutler RG; Laferla FM; Mattson MP. 2007. Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease. Neurobiol Dis 26(1):212-20. [PubMed: 17306982] [MGI Ref ID J:134857]
Hirata-Fukae C; Li HF; Hoe HS; Gray AJ; Minami SS; Hamada K; Niikura T; Hua F; Tsukagoshi-Nagai H; Horikoshi-Sakuraba Y; Mughal M; Rebeck GW; LaFerla FM; Mattson MP; Iwata N; Saido TC; Klein WL; Duff KE; Aisen PS; Matsuoka Y. 2008. Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Brain Res 1216:92-103. [PubMed: 18486110] [MGI Ref ID J:138344]
Janelsins MC; Mastrangelo MA; Park KM; Sudol KL; Narrow WC; Oddo S; LaFerla FM; Callahan LM; Federoff HJ; Bowers WJ. 2008. Chronic neuron-specific tumor necrosis factor-alpha expression enhances the local inflammatory environment ultimately leading to neuronal death in 3xTg-AD mice. Am J Pathol 173(6):1768-82. [PubMed: 18974297] [MGI Ref ID J:143926]
Kitazawa M; Cheng D; Laferla FM. 2009. Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD. J Neurochem 108(6):1550-60. [PubMed: 19183260] [MGI Ref ID J:146855]
Kitazawa M; Green KN; Caccamo A; LaFerla FM. 2006. Genetically augmenting Abeta42 levels in skeletal muscle exacerbates inclusion body myositis-like pathology and motor deficits in transgenic mice. Am J Pathol 168(6):1986-97. [PubMed: 16723713] [MGI Ref ID J:109124]
Kitazawa M; Oddo S; Yamasaki TR; Green KN; LaFerla FM. 2005. Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer's disease. J Neurosci 25(39):8843-53. [PubMed: 16192374] [MGI Ref ID J:101347]
Knuesel I; Nyffeler M; Mormede C; Muhia M; Meyer U; Pietropaolo S; Yee BK; Pryce CR; LaFerla FM; Marighetto A; Feldon J. 2009. Age-related accumulation of Reelin in amyloid-like deposits. Neurobiol Aging 30(5):697-716. [PubMed: 17904250] [MGI Ref ID J:149579]
LaFontaine MA; Mattson MP; Butterfield DA. 2002. Oxidative stress in synaptosomal proteins from mutant presenilin-1 knock-in mice: implications for familial Alzheimer's disease. Neurochem Res 27(5):417-21. [PubMed: 12064358] [MGI Ref ID J:106192]
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]
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]
Ma QL; Yang F; Rosario ER; Ubeda OJ; Beech W; Gant DJ; Chen PP; Hudspeth B; Chen C; Zhao Y; Vinters HV; Frautschy SA; Cole GM. 2009. Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J Neurosci 29(28):9078-89. [PubMed: 19605645] [MGI Ref ID J:151572]
Malik B; Currais A; Soriano S. 2008. Cell cycle-driven neuronal apoptosis specifically linked to amyloid peptide Abeta1-42 exposure is not exacerbated in a mouse model of presenilin-1 familial Alzheimer's disease. J Neurochem 106(2):912-6. [PubMed: 18466334] [MGI Ref ID J:139367]
Mattson MP; Zhu H; Yu J; Kindy MS. 2000. Presenilin-1 mutation increases neuronal vulnerability to focal ischemia in vivo and to hypoxia and glucose deprivation in cell culture: involvement of perturbed calcium homeostasis. J Neurosci 20(4):1358-64. [PubMed: 10662826] [MGI Ref ID J:60290]
Milhavet O; Martindale JL; Camandola S; Chan SL; Gary DS; Cheng A; Holbrook NJ; Mattson MP. 2002. Involvement of Gadd153 in the pathogenic action of presenilin-1 mutations. J Neurochem 83(3):673-81. [PubMed: 12390529] [MGI Ref ID J:79892]
Milton RH; Abeti R; Averaimo S; DeBiasi S; Vitellaro L; Jiang L; Curmi PM; Breit SN; Duchen MR; Mazzanti M. 2008. CLIC1 function is required for beta-amyloid-induced generation of reactive oxygen species by microglia. J Neurosci 28(45):11488-99. [PubMed: 18987185] [MGI Ref ID J:143202]
Oddo S; Caccamo A; Cheng D; Jouleh B; Torp R; LaFerla FM. 2007. Genetically augmenting tau levels does not modulate the onset or progression of Abeta pathology in transgenic mice. J Neurochem 102(4):1053-63. [PubMed: 17472708] [MGI Ref ID J:124130]
Oddo S; Caccamo A; Green KN; Liang K; Tran L; Chen Y; Leslie FM; LaFerla FM. 2005. Chronic nicotine administration exacerbates tau pathology in a transgenic model of Alzheimer's disease. Proc Natl Acad Sci U S A 102(8):3046-51. [PubMed: 15705720] [MGI Ref ID J:96834]
Oddo S; Caccamo A; Kitazawa M; Tseng BP; LaFerla FM. 2003. Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease. Neurobiol Aging 24(8):1063-70. [PubMed: 14643377] [MGI Ref ID J:128565]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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 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]
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]
Berger Z; Roder H; Hanna A; Carlson A; Rangachari V; Yue M; Wszolek Z; Ashe K; Knight J; Dickson D; Andorfer C; Rosenberry TL; Lewis J; Hutton M; Janus C. 2007. Accumulation of pathological tau species and memory loss in a conditional model of tauopathy. J Neurosci 27(14):3650-62. [PubMed: 17409229] [MGI Ref ID J:121178]
Billings LM; Green KN; McGaugh JL; LaFerla FM. 2007. Learning decreases A beta*56 and tau pathology and ameliorates behavioral decline in 3xTg-AD mice. J Neurosci 27(4):751-61. [PubMed: 17251414] [MGI Ref ID J:117782]
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]
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]
Bourasset F; Melissa O; Tremblay C; Julien C; Do TM; Oddo S; LaFerla F; Calon F. 2009. Reduction of the cerebrovascular volume in a transgenic mouse model of Alzheimer's disease. Neuropharmacology 56(4):808-13. [PubMed: 19705573] [MGI Ref ID J:153528]
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]
Caccamo A; Oddo S; Tran LX; Laferla FM. 2007. Lithium Reduces Tau Phosphorylation but Not A{beta} or Working Memory Deficits in a Transgenic Model with Both Plaques and Tangles. Am J Pathol 170(5):1669-78. [PubMed: 17456772] [MGI Ref ID J:121081]
Carroll JC; Rosario ER; Chang L; Stanczyk FZ; Oddo S; LaFerla FM; Pike CJ. 2007. Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice. J Neurosci 27(48):13357-65. [PubMed: 18045930] [MGI Ref ID J:127796]
Chakroborty S; Goussakov I; Miller MB; Stutzmann GE. 2009. Deviant ryanodine receptor-mediated calcium release resets synaptic homeostasis in presymptomatic 3xTg-AD mice. J Neurosci 29(30):9458-70. [PubMed: 19641109] [MGI Ref ID J:151323]
Clinton LK; Billings LM; Green KN; Caccamo A; Ngo J; Oddo S; McGaugh JL; LaFerla FM. 2007. Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice. Neurobiol Dis 28(1):76-82. [PubMed: 17659878] [MGI Ref ID J:134819]
Cruz JC; Tseng HC; Goldman JA; Shih H; Tsai LH. 2003. Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron 40(3):471-83. [PubMed: 14642273] [MGI Ref ID J:104240]
Duce JA; Smith DP; Blake RE; Crouch PJ; Li QX; Masters CL; Trounce IA. 2006. Linker histone H1 binds to disease associated amyloid-like fibrils. J Mol Biol 361(3):493-505. [PubMed: 16854430] [MGI Ref ID J:114872]
Fonseca MI; Ager RR; Chu SH; Yazan O; Sanderson SD; LaFerla FM; Taylor SM; Woodruff TM; Tenner AJ. 2009. Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's disease. J Immunol 183(2):1375-83. [PubMed: 19561098] [MGI Ref ID J:151661]
Green KN; Billings LM; Roozendaal B; McGaugh JL; LaFerla FM. 2006. Glucocorticoids increase amyloid-beta and tau pathology in a mouse model of Alzheimer's disease. J Neurosci 26(35):9047-56. [PubMed: 16943563] [MGI Ref ID J:112193]
Green KN; Martinez-Coria H; Khashwji H; Hall EB; Yurko-Mauro KA; Ellis L; LaFerla FM. 2007. Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-beta and tau pathology via a mechanism involving presenilin 1 levels. J Neurosci 27(16):4385-95. [PubMed: 17442823] [MGI Ref ID J:121088]
Hirata-Fukae C; Li HF; Hoe HS; Gray AJ; Minami SS; Hamada K; Niikura T; Hua F; Tsukagoshi-Nagai H; Horikoshi-Sakuraba Y; Mughal M; Rebeck GW; LaFerla FM; Mattson MP; Iwata N; Saido TC; Klein WL; Duff KE; Aisen PS; Matsuoka Y. 2008. Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Brain Res 1216:92-103. [PubMed: 18486110] [MGI Ref ID J:138344]
Janelsins MC; Mastrangelo MA; Park KM; Sudol KL; Narrow WC; Oddo S; LaFerla FM; Callahan LM; Federoff HJ; Bowers WJ. 2008. Chronic neuron-specific tumor necrosis factor-alpha expression enhances the local inflammatory environment ultimately leading to neuronal death in 3xTg-AD mice. Am J Pathol 173(6):1768-82. [PubMed: 18974297] [MGI Ref ID J:143926]
Kitazawa M; Cheng D; Laferla FM. 2009. Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD. J Neurochem 108(6):1550-60. [PubMed: 19183260] [MGI Ref ID J:146855]
Kitazawa M; Oddo S; Yamasaki TR; Green KN; LaFerla FM. 2005. Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer's disease. J Neurosci 25(39):8843-53. [PubMed: 16192374] [MGI Ref ID J:101347]
Knuesel I; Nyffeler M; Mormede C; Muhia M; Meyer U; Pietropaolo S; Yee BK; Pryce CR; LaFerla FM; Marighetto A; Feldon J. 2009. Age-related accumulation of Reelin in amyloid-like deposits. Neurobiol Aging 30(5):697-716. [PubMed: 17904250] [MGI Ref ID J:149579]
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]
Ma QL; Yang F; Rosario ER; Ubeda OJ; Beech W; Gant DJ; Chen PP; Hudspeth B; Chen C; Zhao Y; Vinters HV; Frautschy SA; Cole GM. 2009. Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J Neurosci 29(28):9078-89. [PubMed: 19605645] [MGI Ref ID J:151572]
Milton RH; Abeti R; Averaimo S; DeBiasi S; Vitellaro L; Jiang L; Curmi PM; Breit SN; Duchen MR; Mazzanti M. 2008. CLIC1 function is required for beta-amyloid-induced generation of reactive oxygen species by microglia. J Neurosci 28(45):11488-99. [PubMed: 18987185] [MGI Ref ID J:143202]
Oddo S; Caccamo A; Cheng D; Jouleh B; Torp R; LaFerla FM. 2007. Genetically augmenting tau levels does not modulate the onset or progression of Abeta pathology in transgenic mice. J Neurochem 102(4):1053-63. [PubMed: 17472708] [MGI Ref ID J:124130]
Oddo S; Caccamo A; Green KN; Liang K; Tran L; Chen Y; Leslie FM; LaFerla FM. 2005. Chronic nicotine administration exacerbates tau pathology in a transgenic model of Alzheimer's disease. Proc Natl Acad Sci U S A 102(8):3046-51. [PubMed: 15705720] [MGI Ref ID J:96834]
Oddo S; Caccamo A; Kitazawa M; Tseng BP; LaFerla FM. 2003. Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease. Neurobiol Aging 24(8):1063-70. [PubMed: 14643377] [MGI Ref ID J:128565]
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]
Parachikova A; Cotman CW. 2007. Reduced CXCL12/CXCR4 results in impaired learning and is downregulated in a mouse model of Alzheimer disease. Neurobiol Dis 28(2):143-53. [PubMed: 17764962] [MGI Ref ID J:134804]
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]
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]
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]
Rohn TT; Vyas V; Hernandez-Estrada T; Nichol KE; Christie LA; Head E. 2008. Lack of pathology in a triple transgenic mouse model of Alzheimer's disease after overexpression of the anti-apoptotic protein Bcl-2. J Neurosci 28(12):3051-9. [PubMed: 18354008] [MGI Ref ID J:133211]
Rosario ER; Carroll JC; Oddo S; LaFerla FM; Pike CJ. 2006. Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer's disease. J Neurosci 26(51):13384-9. [PubMed: 17182789] [MGI Ref ID J:116683]
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]
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]
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]
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]
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]
Yang Y; Varvel NH; Lamb BT; Herrup K. 2006. Ectopic cell cycle events link human Alzheimer's disease and amyloid precursor protein transgenic mouse models. J Neurosci 26(3):775-84. [PubMed: 16421297] [MGI Ref ID J:104514]
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]
Yao PJ; Bushlin I; Furukawa K. 2005. Preserved synaptic vesicle recycling in hippocampal neurons in a mouse Alzheimer's disease model. Biochem Biophys Res Commun 330(1):34-8. [PubMed: 15781228] [MGI Ref ID J:97468]
Health & husbandry
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Colony Maintenance
Breeding & Husbandry When maintaining a live colony, mice that are homozygous for the Psen1 mutation and homozygous for the co-injected APPSwe and tauP301L transgenes (Tg(APPSwe,tauP301L)1Lfa) may be bred together. Mating System See above Diet Information LabDiet® 5K52/5K67
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| Standard Supply | Under Development for Distribution Colony |
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Control Information
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
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