Research Models
Selected Results
3 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 (3) |
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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 | ||||
MAPT V337M, Tg214 | B6SJL/F1 | MAPT | MAPT V337M | Human 4-repeat tau driven by the PDGF-β promoter. Tagged with myc and Flag on the N- and C-terminals respectively. | MAPT: Transgenic | Alzheimer's Disease, Frontotemporal Dementia | SDS-insoluble tau aggregates in hippocampus. Degenerating neurons in the hippocampus containing phosphorylated and ubiquitinated tau aggregates with β-sheet structure. | Higher overall spontaneous locomotion than non-transgenic littermates in elevated plus maze. No differences in the Morris water maze. | The amount of mutant tau varied, but was generally less than one tenth of endogenous tau levels. In hippocampal slices there was attenuation of the Schaffer collateral-evoked neural response. | Unknown | Tanemura et al., 2002, Tanemura et al., 2001 | 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 |
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+.
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. |
Tau V337M
Observed
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Tangles at 48
Fibrillar staining in the hippocampus of 11 month old animals by Congo red birefringence. Absent in 4 month old mice, indicating the formation of these neurofilament-like structures occurs between 4 and 11 months (Tanemura et al., 2001).
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Neuronal Loss at 43
Evidence of hippocampal neuronal degeneration in 10 month old animals: irregularly shaped neurons with tau pathology that stained with propidium iodide. As characteristics of apoptosis were not observed, the neurons were thought to be undergoing non-apoptotic atrophic degeneration (Tanemura et al., 2002).
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Changes in LTP/LTD at 65
In hippocampal slices there was an attenuation of the amplitude of Schaffer collateral evoked hippocampal depolarization (Tanemura et al., 2002).
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Cognitive Impairment at 48
Behavioral abnormalities measured in 11 month-old mice. They spent more time in the open arms of the elevated plus maze and had greater overall locomoter activity. No differences in the Morris water maze compared with non-transgenic mice, suggesting the transgenic animals retain spatial recognition abilities (Tanemura et al., 2002).
Absent
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Plaques at
Absent.
No Data
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Gliosis at
Unknown.
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Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
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MAPT | MAPT V337M | MAPT: Transgenic | Alzheimer's Disease, Frontotemporal Dementia | SDS-insoluble tau aggregates in hippocampus. Degenerating neurons in the hippocampus containing phosphorylated and ubiquitinated tau aggregates with β-sheet structure. |
Higher overall spontaneous locomotion than non-transgenic littermates in elevated plus maze. No differences in the Morris water maze. |
TMHT (Thy-1 mutated human tau)
Observed
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Tangles at 17
Tangles at 4 months and progress with age.
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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). |