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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APPNL-F/NL-F | Apptm2.1Tcs/Apptm2.1Tcs | C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP I716F (Iberian) | Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and the Swedish and Beyreuther/Iberian mutations. | APP: Knock-In | Alzheimer's Disease | Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. | Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze. | No overexpression of APP. Generates wild-type levels of AICD. | Available through Takaomi Saido | Saito et al., 2014 | Yes | ||
APPNL-G-F/NL-G-F, AppNL-G-F | Apptm3.1Tcs/Apptm3.1Tcs | C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic) | Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and three pathogenic mutations (Swedish, Beyreuther/Iberian, and Arctic). | APP: Knock-In | Alzheimer's Disease | Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. | Memory impairment by 6 months as measured by the Y maze. | No overexpression of APP. Wild-type levels of AICD. | Available through Takaomi Saido | Saito et al., 2014 | 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+.
APP NL-F Knock-in
Observed
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Plaques at 26
Homozygotes develop amyloid plaques starting at 6 months in the cortex and hippocampus. Heterozygotes develop amyloidosis after 24 months. Plaques contained Aβ1-42 and pyroglutamate Aβ (Aβ3(pE)-42); Aβx-40 was a minor species.
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Gliosis at 26
Microglia and activated astrocytes accumulate with age, starting around 6 months of age, concurrent with plaque formation.
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Synaptic Loss at 39
Reduced synaptophysin and PSD95 immunoreactivities associated with Aβ plaques at 9-12 months.
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Cognitive Impairment at 78
Memory impairment in homozygous mice at 18 months as measured by the Y maze test. APPNL/NL mice (with Swedish mutation only) were unimpaired at this age. No significant deficit was seen in the Morris water maze at 18 months.
Absent
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Tangles at
Absent; although elevated levels of phosphorylated tau are observed in dystrophic neurites around plaques.
-
Neuronal Loss at
Absent.
No Data
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP I716F (Iberian) | APP: Knock-In | Alzheimer's Disease | Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. |
Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze. |
APP NL-G-F Knock-in
Observed
-
Plaques at 9
Aggressive amyloidosis; plaques develop in homozygous mice starting at 2 months with near saturation by 7 months. Aβ deposition at 4 months in heterozygous mice. Cortical and subcortical amyloidosis present.
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Gliosis at 9
Microglia and activated astrocytes accumulate with age starting around 2 months, especially around plaques in a manner concurrent with plaque formation.
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Synaptic Loss at 17
Reduction of synaptophysin and PSD95 immunoreactivities associated with Aβ plaques in both cortical and hippocampal areas.
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Cognitive Impairment at 26
Memory impairment in homozygous mice by 6 months of age as measured by the Y maze.
Absent
-
Tangles at
Absent; although phosphorylated tau is elevated in dystrophic neurites around plaques.
-
Neuronal Loss at
Absent.
No Data
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic) | APP: Knock-In | Alzheimer's Disease | Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. |
Memory impairment by 6 months as measured by the Y maze. |