Research Models
Selected Results
6 Models
Name | Other Names | Strain Name | Genetic Background | Gene | Mutation | Modification Info | Modification | Disease | Neuropathology | Behavior/Cognition | Other Phenotype | Availability | Primary Paper | Visualization | |
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Mouse Models (6) |
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3xTg-AD, The LaFerla mouse | B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax | C7BL/6;129X1/SvJ;129S1/Sv | Psen1, APP, MAPT | APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN1 M146V | Single-cell embryos from mice with knock-in of PSEN1 with the PS1M146V mutation were injected with two human transgenes (APP with the Swedish mutation and MAPT with the P30IL mutation). Transgenes integrated at a single locus under the control of the mouse Thy1.2 promoter. | Psen1: Knock-In; APP: Transgenic; MAPT: Transgenic | Alzheimer's Disease | Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles. | Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task. | The Jackson Lab; available through the JAX MMRRC Stock# 034830; Live | Oddo et al., 2003 | Yes | |||
B6;CB-Tg(Thy1-PSEN1*M146V/Thy1-APP*swe)10Arte | Co-injection of transgenes into B6CBF1 oocytes, back-crossed to C57BL/6 | APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 M146V | Co-integration of two transgenes, mutant APP carrying the K670N/M671L mutation, and mutant PSEN1 carrying the M146V mutation, both under the control of the Thy-1 promoter. | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Robust early plaque development (by 3 months in homozygotes, 5 months in hemizygotes), predominantly congophilic dense-core amyloid plaques surrounded by dystrophic neurites and gliosis. Some diffuse plaques and cerebral amyloidosis. No tau tangles. Neurons have reduced dendritic length, surface area, and branches. | Age-related learning and memory deficits, especially episodic memory, in select paradigm-specific tasks by 12 months. | Good breeding capabilities and no premature death. | Taconic: Stock #16347 | Willuweit et al., 2009 | Yes | |||
PSEN1(M146V) (line 8.9) | Swiss Webster x B6D2F1 | PSEN1 | PSEN1 M146V | Transgene containing human PSEN1 with the M146V mutation driven by the rat PDGF-β promoter. | PSEN1: Transgenic | Alzheimer's Disease | No abnormal neuropathology up to 2.5 years. Elevated Aβ42(43). Altered mitochondrial activity and disregulation of calcium homeostasis. | Unknown. | Medium and late after hyperpolarizations in CA3 pyramidal cells were larger compared with nontransgenic or mice transgenic for wild-type PSEN1. | Available through the Technology Transfer Office, Patents & Licensing, University of South Florida | Duff et al., 1996 | No | |||
PS1M146V KI, PS1M146VKI, The Miles W. Miller Mouse | B6.129-Psen1tm1Mpm/J | C57BL/6 | PSEN1 | PSEN1 M146V | Point mutations were introduced into exon 5 of the endogenous mouse PSEN1 gene altering the codons corresponding to amino acids 145 and 146 from isoleucine and methionine to valine and valine, respectively. The targeting vector contained a lox-P flanked neomycin resistance cassette and herpes simplex virus thymidine kinase genes. | PSEN1: Knock-In | Alzheimer's Disease | Hypersensitive to kainate-induced degeneration and death of CA3, CA1 and hilar neurons. Cultured hippocampal neurons have increased vulnerability to death induced by glutamate. Disrupted calcium homeostasis. Increased oxidative stress and mitochondrial dysfunction. | Unknown. | Mice are viable, fertile, and normal in size. No gross physical or behavioral abnormalities. | The Jackson Lab: Stock# 004193; Cryopreserved | Guo et al., 1999 | No | ||
TAS10 x TPM, APPswe x PS1.M1466V, TAS/TPM | TAS10 transgene originally injected into C57BL/6 x C3H oocytes, with some backcrossing to C57BL/6. TPM generated on pure C57BL/6 background. | APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 M146V | This is a double transgenic model generated by crossing TAS10 mice (an APP transgenic line expressing human APP695 with the Swedish mutation) with TPM mice (a PSEN1 transgenic expressing human PSEN1 with the M146V mutation). Both transgenes are driven by the murine Thy-1 promoter. | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Aβ deposits beginning at 3 months of age, with fibrillar plaques by 6 months in the cerebral cortex and hippocampus. Some vascular amyloid. Plaques surrounded by dystrophic neurites and reactive glia. No tangles or neuronal loss. Female mice have more rapid and severe amyloid pathology. | Age-dependent impairment in object recognition memory starting around 6 months of age. | Unknown | Howlett et al., 2004 | Yes | ||||
Thy-1 PS1.M146V | Transgene injected into fertilized oocytes from pure C57BL/6 mice. | PSEN1 | PSEN1 M146V | Transgene encoding human PSEN1 carrying the M146V mutation. Transgene is driven by the murine Thy-1 promoter. | PSEN1: Transgenic | Alzheimer's Disease | No plaques. | Unknown. | Unknown | Howlett et al., 2004 | No |
3 Visualizations
AD-related Research Models
Phenotypes Examined
- Plaques
- Tangles
- Neuronal Loss
- Gliosis
- Synaptic Loss
- Changes in LTP/LTD
- Cognitive Impairment
When visualized, these phenotypes will distributed over a 18 month timeline demarcated at the following intervals: 3mo, 6mo, 9mo, 1yr, 15mo, 18mo+.
3xTg
Observed
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Plaques at 26
Extracellular Aβ deposits by 6 months in the frontal cortex, predominantly layers 4 and 5 and progress with age (Oddo et al., 2003).
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Tangles at 52
By 12 months extensive tau immunoreactivity in CA1 neurons of the hippocampus, particularly pyramidal neurons, later in the cortex. No tau pathology at 6 months (Oddo et al., 2003).
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Gliosis at 30
Increased density of GFAP immunoreactive astrocytes and IBA-1 immunoreactive microglia compared with wild-type mice at 7 months (Caruso et al., 2013). Development of gliosis may occur earlier.
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Changes in LTP/LTD at 26
By 6 months decreased LTP compared with wild type controls. Impairment in basal synaptic transmission. No change at 1 month of age (Oddo et al., 2003).
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Cognitive Impairment at 17
Cognitive impairment manifests at 4 months as a deficit in long-term retention and correlates with the accumulation of intraneuronal Aβ in the hippocampus and amygdala, but plaques and tangles are not yet apparent (Billings et al., 2005).
Absent
No Data
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Neuronal Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
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Psen1, APP, MAPT | APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN1 M146V | Psen1: Knock-In; APP: Transgenic; MAPT: Transgenic | Alzheimer's Disease | Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles. |
Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task. |
ARTE10
Observed
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Plaques at 13
Robust and reliable plaque pathology as early as 3 months in homozygotes, 5 months in hemizygotes. Plaques start in the anterior neocortex and subiculum, spreading to other brain regions (e.g. hippocampus, thalamus, amygdala). Congophilic dense-core plaques are abundant, with lower levels of diffuse plaques and some cerebral amyloid angiopathy.
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Gliosis at 22
Glial activation, including reactive astrocytes and activated microglia, is present in areas around plaques by 5 months of age in homozygous animals, later in hemizygotes.
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Synaptic Loss at 13
Decreased expression of synaptophysin mRNA in the brain by 3-4 months of age in both hemizygous and homozygous animals.
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Cognitive Impairment at 52
Select, paradigm-dependent, deficits in learning and memory, especially episodic memory, by 12 months in homozygous and hemizygous mice.
Absent
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Tangles at
No tangles or neuropil threads, but some hyperphosphorylated tau by eight months in dystrophic neurites.
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Neuronal Loss at
Outright neuronal loss has not been documented, but substantial degeneration of dendritic arbors occurs by 10-14 months of age in hippocampal neurons.
No Data
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Changes in LTP/LTD at
Unknown; however, hippocampal neurons exhibit substantial changes in electrophysiological properties by 10-14 months of age, including hyperexcitability in the form of increased firing of action potentials and a more efficient transition from solitary firing to bursting.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
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APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 M146V | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Robust early plaque development (by 3 months in homozygotes, 5 months in hemizygotes), predominantly congophilic dense-core amyloid plaques surrounded by dystrophic neurites and gliosis. Some diffuse plaques and cerebral amyloidosis. No tau tangles. Neurons have reduced dendritic length, surface area, and branches. |
Age-related learning and memory deficits, especially episodic memory, in select paradigm-specific tasks by 12 months. |
TASTPM (TAS10 x TPM)
Observed
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Plaques at 26
Aβ begins to deposit at 3 months of age, with fibrillar plaques evident by 6 months in the cerebral cortex and hippocampus. Some vascular amyloid is also observed. Plaque pathology is more severe in female mice.
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Gliosis at 28
Greater numbers of reactive astrocytes and microglia by 6 months of age in the hippocampus and cortex, predominantly near amyloid plaques.
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Cognitive Impairment at 26
Age-dependent impairment in object recognition memory starting around 6 months of age for both sexes. No impairment at 3 to 4 months of age.
Absent
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Tangles at
Absent.
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Neuronal Loss at
Minimal neuronal loss up to 10 months of age. Some signs of loss in the immediate vicinity of plaques in the hippocampus (Howlett et al., 2008).
No Data
-
Synaptic Loss at
Unknown.
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Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 M146V | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Aβ deposits beginning at 3 months of age, with fibrillar plaques by 6 months in the cerebral cortex and hippocampus. Some vascular amyloid. Plaques surrounded by dystrophic neurites and reactive glia. No tangles or neuronal loss. Female mice have more rapid and severe amyloid pathology. |
Age-dependent impairment in object recognition memory starting around 6 months of age. |