Research Models

Selected Results

1 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 (1)
<p>“Proaggregation mutant”</p>, <p>TauRDΔ</p>, <p>TauRD</p>, <p>TauRD/ΔK280</p>, <p>TauRDΔK</p> C57BL/6 MAPT MAPT K280del Regulatable expression of an abbreviated human tau sequence (amino acids 244-372) encompassing the four microtubule-binding repeat domains and carrying the ΔK280 mutation. Transgene is driven by the forebrain-specific CAMKIIα promoter. TET-OFF system in which the transgene is regulated by the tetracycline transactivator (tTA) and turned off by administration of doxycycline. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Tau aggregates and tangles as early as 2-3 months after gene expression. Gallyas silver-positive neurons abundant in the entorhinal cortex and amygdala, spreading to the neocortex by 15 months. “Ballooned” neurons. Astrogliosis. Synaptic structural changes and reduced synaptic number. Hippocampal neuronal loss. Reversible learning and memory deficits in the Morris water maze and passive avoidance test. No significant motor deficit, although slight reduction in Rotarod performance. Missorting of tau into the somato-dendritic compartment. Calcium dysregulation at synaptic boutons. Deficits in synaptic plasticity, including LTP and LTD. Unknown Mocanu et al., 2008 Yes

1 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+.

TauRDΔK280 (“Proaggregation mutant”)

Observed
  1. X
    Tangles at 9

    Tau tangles and aggregates with as little as 2-3 months of transgene expression. Tangles start in the entorhinal cortex and amygdala and spread to the neocortex by 15 months. Heterogeneous tangle morphology, including flame-shaped.

  2. X
    Neuronal Loss at 22

    Neuronal loss in the dentate gyrus (granule neurons) following 5 months of transgene expression. Shrinkage of the molecular layer of the hippocampus.

  3. X
    Gliosis at 91

    Astrogliosis in the hilus region of the hippocampus after 21 months of transgene expression. Additional increases in GFAP-positive astrocytes in the entorhinal and piriform cortices.

  4. X
    Synaptic Loss at 41

    Hippocampal synaptic loss as indicated by multiple measures following 9.5 months of transgene expression. Reduced synaptophysin immunoreactivity and reduced number of spine synapses as measured by electron microscopy.

  5. X
    Changes in LTP/LTD at 43

    Multiple deficits in synaptic plasticity, including deficits in LTP and LTD, after 10 months of transgene expression. Functional changes are associated with structural synaptic changes, local calcium dysregulation, and a decrease in the synaptic vesicle pool.

  6. X
    Cognitive Impairment at 43

    Learning and memory impairments are apparent after 10 months of transgene expression as assessed by the Morris water maze and passive avoidance tasks.

Absent
  • Plaques at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT K280del MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia

Tau aggregates and tangles as early as 2-3 months after gene expression. Gallyas silver-positive neurons abundant in the entorhinal cortex and amygdala, spreading to the neocortex by 15 months. “Ballooned” neurons. Astrogliosis. Synaptic structural changes and reduced synaptic number. Hippocampal neuronal loss.

Reversible learning and memory deficits in the Morris water maze and passive avoidance test. No significant motor deficit, although slight reduction in Rotarod performance.

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