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
Mouse Models (3)
happ-SL x hTau, APP751-SL x TAU441 V337M R406W C57BL/6 x DBA MAPT, APP APP KM670/671NL (Swedish), APP V717I (London), MAPT V337M (Seattle), 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 (Seattle) 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 (Seattle), 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
  1. X
    Plaques at 13

    Plaques start at 3 months in the frontal cortex and become more widespread with age.

  2. X
    Gliosis at 26

    Microglial activation. Numerous glial cells around amyloid plaques at 6 months.

  3. X
    Cognitive Impairment at 13

    Cognitive impairment at 3 months demonstrated by Morris Water Maze.

Absent
No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT, APP APP KM670/671NL (Swedish), APP V717I (London), MAPT V337M (Seattle), 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.

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Tau V337M

Observed
  1. X
    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).

  2. X
    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).

  3. X
    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).

  4. X
    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
  • Plaques at

    Absent.

No Data
  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT V337M (Seattle) 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.

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TMHT (Thy-1 mutated human tau)

Observed
  1. X
    Tangles at 17

    Tangles at 4 months and progress with age.

  2. X
    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
MAPT MAPT V337M (Seattle), 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).

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