Research Models
Selected Results
5 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 (5) |
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happ-SL x hTau, APP751-SL x TAU441 V337M R406W | C57BL/6 x DBA | MAPT, APP | APP K670_M671delinsNL (Swedish), APP V717I (London), MAPT V337M, MAPT R406W | Cross of two models from QPS: (1) APP751SL, which overexpresses mutant human APP (isoform 751) with the Swedish (K670N/M671L) and London (V717I) mutations under the control of the brain-specific Thy1 promoter, and (2) THMT, which overexpresses human MAPT (441) with the V337M and R406W mutations under the control of Thy1. | MAPT: Transgenic; APP: Transgenic | Alzheimer's Disease | Plaques start at 3-6 months. Some acceleration of amyloid deposition in the amygdala as compared to the hAPPSL single transgenic; detected in bigenic animals by 3 months vs 6 months. | Cognitive impairment at 3 months demonstrated by the Morris Water Maze. | Eyes appear smaller compared to wild-type mice, but pupillary reflex, eye blink reflex, and visual test performance are normal. | QPS-Austria | Yes | ||||
hAPP/hTau/hPS1, PLB1(Triple) | C57BL6 | APP, MAPT, PSEN1 | APP V717I (London), APP K670_M671delinsNL (Swedish), PSEN1 A246E, MAPT P301L, MAPT R406W | Targeted insertion of human APP and tau sequences at the HPRT site on the X chromosome, driven by mouse CaMKII-α. Human APP (isoform 770) with the Swedish and London mutations. Human tau (isoform 2N/4R, 441 amino acids) with P301L and R406W. APP/tau-expressing animals (PLB1-double) were crossed with hPS1 (A246E) transgenic mice (Borchelt et al., 1997) to generate the triple transgenic. | APP: Multi-transgene; MAPT: Multi-transgene; PSEN1: Multi-transgene | Alzheimer's Disease | Age-related neuropathology including intraneuronal and oligomeric Aβ accumulation and hyperphosphorylated tau in the hippocampus and cortex from six months. Minimal amyloid plaques up to 21 months. Subtle tau pathology, but no overt tangles. Cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain by FDG-PET/CT. | Cognitive deficits in recognition memory and spatial learning emerging between five and 12 months. Impairments in hippocampal plasticity. | Litter size and overall health were normal. Mice spent more time awake at six months and had fragmented sleep. Quantitative EEG showed heightened delta power during wakefulness and REM sleep. | Available through Bettina Platt | Platt et al., 2011 | Yes | |||
Tau R406W-Prp | C57BL6 x C3H, maintained in B6C3 background | MAPT | MAPT R406W | Human tau with the R406W mutation driven by the mouse prion protein promoter. | MAPT: Transgenic | Frontotemporal Dementia | Age-dependent increase in tau. Neurofibrillary-tangle-like pathology (filamentous intraneuronal tau aggregates), especially in the hippocampus. Neurodegeneration. Extensive gliosis in the brain and spinal cord. | Progressive motor weakness with advancing age, as demonstrated by dystonic movements of the hindlimbs when lifted by the tail. | Altered microtubule binding and slow axonal transport of tau. Reduced lifespan. | Unknown | Zhang et al., 2004 | No | |||
TgTauR406W, Tau R406W-CAMKII | B6SJL/F1; backcrossed to C57BL/6J | MAPT | MAPT R406W | Human 4-repeat tau cDNA with the R406W mutation containing myc and FLAG tags at N-and C-terminal ends, respectively, and driven by the CaMK-II promoter. | MAPT: Transgenic | Frontotemporal Dementia, Alzheimer's Disease | Argyrophilic and congophilic tau inclusions in neurons of the forebrain with age. Detectable with Congo red, thioflavin-S and Gallyas silver stain. Congophilic tau inclusions also in the hippocampus and amygdala. Mainly straight tau filaments. | Impairments in contextual and cued fear conditioning at 16–23 months compared with wild-type littermates. No detectable sensorimotor deficits. | No differences from wild-type in body weight, sensorimotor reflexes (acoustic startle response), or motor coordination (accelerating rotarod and pole tests). Attenuation of the Schaffer collateral-evoked neural response in hippocampal slices. Decrease in prepulse inhibition. Higher mortality. | Unknown | Tatebayashi et al., 2002 | Yes | |||
Thy-1 mutated human tau, TAU 441, hTAU441, TAU441 V337M R406W | C57Bl/6xDBA | MAPT | MAPT V337M, MAPT R406W | Transgene consists of human MAPT Tau441 (2N/4R) with mutations V337M and R406W under control of the Thy1 promoter. | MAPT: Transgenic | Alzheimer's Disease | Increased total tau, and phosphorylated tau (Thr181, Ser199, Thr231) in amygdala and hippocampus starting at 3 months. | Spatial memory deficits starting at 5 months (Morris water maze). Olfactory deficits at 5 months (Buried food test). No motor deficits (rota rod, beam walk) or depressive behavior (forced swim test). | Olfactory deficits. | The CRO QPS-Austria offers research services with this line. | Flunkert et al., 2013 | Yes |
4 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+.
APP751-SL x THMT
Observed
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Plaques at 13
Plaques start at 3 months in the frontal cortex and become more widespread with age.
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Gliosis at 26
Microglial activation. Numerous glial cells around amyloid plaques at 6 months.
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Cognitive Impairment at 13
Cognitive impairment at 3 months demonstrated by Morris Water Maze.
Absent
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
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MAPT, APP | APP K670_M671delinsNL (Swedish), APP V717I (London), MAPT V337M, MAPT R406W | MAPT: Transgenic; APP: Transgenic | Alzheimer's Disease | Plaques start at 3-6 months. Some acceleration of amyloid deposition in the amygdala as compared to the hAPPSL single transgenic; detected in bigenic animals by 3 months vs 6 months. |
Cognitive impairment at 3 months demonstrated by the Morris Water Maze. |
PLB1-triple (hAPP/hTau/hPS1)
Observed
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Gliosis at 52
Increased inflammation (GFAP labelling) detected at 12 months in cortex and hippocampus (Platt, unpublished observation).
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Changes in LTP/LTD at 26
Impairments in long-term and short-term hippocampal plasticity. LTP following theta-burst stimulation decayed faster and paired-pulse facilitation was reduced relative to wild-type mice at both six and 12 months of age. Synaptic transmission impacted at 12 months.
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Cognitive Impairment at 22
Social recognition memory was impaired by five months and further impaired by 12 months. Similarly, object recognition memory was impaired by eight months. Spatial learning impairments were seen later; at 12 months deficits in spatial acquisition learning were seen in the open field water maze that were not apparent at 5 months.
Absent
-
Plaques at
Sparse plaques out to 21 months of age. Only marginally increased compared with wild-types and overall very low compared to over-expression models. However, Aβ accumulated intracellularly and also formed oligomers.
-
Tangles at
No overt tangle pathology; however, hyyperphosphorylated tau accumulated in the hippocampus and cortex from six months of age.
-
Neuronal Loss at
Absent.
No Data
-
Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
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APP, MAPT, PSEN1 | APP V717I (London), APP K670_M671delinsNL (Swedish), PSEN1 A246E, MAPT P301L, MAPT R406W | APP: Multi-transgene; MAPT: Multi-transgene; PSEN1: Multi-transgene | Alzheimer's Disease | Age-related neuropathology including intraneuronal and oligomeric Aβ accumulation and hyperphosphorylated tau in the hippocampus and cortex from six months. Minimal amyloid plaques up to 21 months. Subtle tau pathology, but no overt tangles. Cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain by FDG-PET/CT. |
Cognitive deficits in recognition memory and spatial learning emerging between five and 12 months. Impairments in hippocampal plasticity. |
Tau R406W transgenic
Observed
-
Tangles at 78
Congophilic tau inclusions in a subset of forebrain neurons around 18 months of age. Detected by Congo red, thioflavin S, and Gallyas silver stain.
-
Cognitive Impairment at 70
Impairments in the contextual and cued fear conditioning test at 16–23 months compared with wild-type littermates. No detectable sensorimotor deficits.
Absent
-
Plaques at
Absent.
No Data
-
Neuronal Loss at
Unknown.
-
Gliosis at
Unknown.
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
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MAPT | MAPT R406W | MAPT: Transgenic | Frontotemporal Dementia, Alzheimer's Disease | Argyrophilic and congophilic tau inclusions in neurons of the forebrain with age. Detectable with Congo red, thioflavin-S and Gallyas silver stain. Congophilic tau inclusions also in the hippocampus and amygdala. Mainly straight tau filaments. |
Impairments in contextual and cued fear conditioning at 16–23 months compared with wild-type littermates. No detectable sensorimotor deficits. |
TMHT (Thy-1 mutated human tau)
Observed
-
Tangles at 17
Tangles at 4 months and progress with age.
-
Cognitive Impairment at 22
Cognitive impairment by 5 months as measured by the Morris Water Maze.
Absent
-
Plaques at
Absent.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
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MAPT | MAPT V337M, MAPT R406W | MAPT: Transgenic | Alzheimer's Disease | Increased total tau, and phosphorylated tau (Thr181, Ser199, Thr231) in amygdala and hippocampus starting at 3 months. |
Spatial memory deficits starting at 5 months (Morris water maze). Olfactory deficits at 5 months (Buried food test). No motor deficits (rota rod, beam walk) or depressive behavior (forced swim test). |