Research Models
Selected Results
2 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 (2) |
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CaMKII-tTA/TRE-hTau-A152T | C57BL/6-Tg(tetO-MAPT*A152T)L1Lms/J | C59Bl/6J | MAPT | MAPT A152T | These bigenic mice use the CaMKIIα promoter to drive expression of tetracycline transactivator (tTA) in forebrain neurons. The responder transgene is the 1N4R isoform of human tau with the A152T mutation. Expression is constitutive unless suppressed by doxycycline. | MAPT: Transgenic | Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy | Tangles or dense tau inclusions not observed. Abnormal accumulations of soluble tau. Age-dependent neuronal loss was observed in the hippocampus. | Age-dependent learning and memory deficits in the Morris water maze. Nest building impaired. Social interaction, anxiety, exploratory behavior, and motor functions were normal. | Increase in basal synaptic activity and epileptiform spikes. Life span normal. | Available as single transgenics: The Jackson Lab Stock# 028979 (cyropreserved) and Stock# 007004 (live) | Maeda et al., 2016 | Yes | ||
hTau40-AT, Ala152T-Tau, A152T-Tau, Tau/A152T | C57BL/6 | MAPT | MAPT A152T | Human full-length tau (hTau40) isoform 2N4R with the A152T mutation expressed under the Thy1.2 promotor is located in the ROSA26 locus. | MAPT: Knock-In | Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy | Tangles in hippocampus, cortex, and spinal cord at 3 months with age-dependent increases. Tau hyperphosphorylation, conformation changes, and mislocalization observed. Age-dependent loss of synapses. | Age-dependent learning and memory deficits in the Morris water maze. Motor functions normal. | Increase in basal synaptic transmission. | Available through Eva Mandelkow | Decker et al., 2016, Sydow et al., 2016 | Yes |
2 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+.
hTau-A152T
Observed
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Neuronal Loss at 87
Neuron loss in the hippocampus was observed by 20 months.
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Gliosis at 17
Astrocytosis, but no differences in microglia.
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Cognitive Impairment at 74
In the Morris water maze, performance was impaired after 17 months of age. Nest building was impaired at 10-14 months. Social interaction, anxiety, exploratory behavior, and motor functions were unaltered.
Absent
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Tangles at
Abnormal accumulations of soluble tau were observed, but not tangles or tangle-like structures.
-
Changes in LTP/LTD at
Unchanged at 20 months.
No Data
-
Plaques at
No data.
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Synaptic Loss at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
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MAPT | MAPT A152T | MAPT: Transgenic | Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy | Tangles or dense tau inclusions not observed. Abnormal accumulations of soluble tau. Age-dependent neuronal loss was observed in the hippocampus. |
Age-dependent learning and memory deficits in the Morris water maze. Nest building impaired. Social interaction, anxiety, exploratory behavior, and motor functions were normal. |
hTau-AT (hTau40-AT)
Observed
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Tangles at 13
Tangles in hippocampus, cortex, and spinal cord starting at 3 months with age-dependent increases. Hyperphosphorylation, conformation changes, and mislocalization.
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Neuronal Loss at 52
Neuron loss in the hippocampus and cortex at 12 months.
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Gliosis at 43
Astrocytosis and microgliosis at 10 months.
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Synaptic Loss at 87
Synaptophysin, but not PSD95, decreased in hippocampus and cortex at 12 months. By Golgi staining, spines unchanged in CA1 at 10 months, increased in CA3 at 12 months, and decreased in CA1 and CA3 at 16 months.
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Cognitive Impairment at 70
No change at 10 months but at 16 months deficits in learning and memory (Morris water maze).
Absent
-
Changes in LTP/LTD at
Unchanged at 12 months.
No Data
-
Plaques at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT | MAPT A152T | MAPT: Knock-In | Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy | Tangles in hippocampus, cortex, and spinal cord at 3 months with age-dependent increases. Tau hyperphosphorylation, conformation changes, and mislocalization observed. Age-dependent loss of synapses. |
Age-dependent learning and memory deficits in the Morris water maze. Motor functions normal. |