Research Models
Selected Results
7 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 (7) |
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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 | ||
AppNL-G-F/MAPT double knock-in, AppNL-G-F/MAPT dKI | C57BL/6J | App, MAPT | APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic) | AppNL-G-F mice (mouse App sequence modified to contain a humanized Aβ region and the Swedish, Iberian, and Arctic mutations linked to AD) were crossed with MAPT knock-in mice (entire genomic sequence of murine Mapt, from exon 1 to exon 14, replaced with the human MAPT gene from the ATG codon of exon 1 to the 3'-untranslated region). | App: Knock-In; MAPT: Knock-In | Alzheimer's Disease | Amyloid plaques, plaque-associated neuritic dystrophy, and neuroinflammation, similar to AppNL-G-F. | Deficits in the Y-maze test of working memory, similar to AppNL-G-F. | Compared with AppNL-G-F mice, AppNL-G-F/MAPT double knock-in mice showed accelerated propagation of pathological tau species after AD-derived tau was injected into the mouse brain. | Available through Takaomi Saido, RIKEN Center for Brain Science. | Saito et al., 2019, Hashimoto et al., 2019 | Yes | |||
AppSAA, AppSAA Knock-in, AppSAA KI, APP-SAA KI, hAbetaSAA, hAbetaSwe,Arc,Aus | B6(Cg)-Apptm1.1Dnli/J | C57BL/6J | App | APP K670_M671delinsNL (Swedish), APP E693G (Arctic), APP T714I (Austrian) | Homologous recombination was used to humanize the Aβ sequence and introduce the FAD-linked Swedish, Arctic, and Austrian mutations into the murine App gene. | App: Knock-In | Alzheimer's Disease | Homozygotes: Amyloid plaques and plaque-associated microgliosis from 4 months of age; cerebral amyloid angiopathy and dystrophic neurites from 8 months of age. Heterozygotes: Amyloid plaques at 16 months of age. | Unknown. | Increased levels of CSF total tau and neurofilament light chain in AppSAA homozygous mice at 8 months of age. Significant alterations of the transcriptomes and lipidomes in microglia of AppSAA homozygotes. | Available from The Jackson Laboratory Stock# 034711. | Xia et al., 2021 | Yes | ||
APPSw/Ind/Arc, APPSwedish/Indiana/Arctic, hAPP Arc line | Inbred C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana), APP E693G (Arctic) | A human APP minigene with the Swedish, Indiana, and Arctic mutations driven by the platelet-derived growth factor β-chain promoter. | APP: Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy | Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20. | At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform. | Premature lethality. Trend toward hyperactivity. Reduced calbindin and Fos levels in the dentate gyrus. | Cryopreserved. Contact Lennart Mucke | Cheng et al., 2004 | Yes | |||
arcAbeta | Origin: B6D2 F1 | APP | APP K670_M671delinsNL (Swedish), APP E693G (Arctic) | Human APP695 transgene containing the Swedish (K670N/M671L) and Arctic mutation (E693G) was generated by site-directed mutagenesis. | APP: Transgenic | Alzheimer's Disease | At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma. | Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze. | Deficits in synaptic plasticity, LTP, and functional connectivity as measured by resting-state fMRI. | Unknown | Knobloch et al., 2007 | Yes | |||
B6CBA-Tg(Thy1.2-hAPParc) | C57BL/6-CBA | APP | APP E693G (Arctic) | Transgenic mice with human APP (isoform 695) bearing the Arctic APP mutation (E693G). | APP: Transgenic | Alzheimer's Disease | Mild amyloid pathology with a relatively late onset, starting with intracellular Aβ, then diffuse extracellular Aβ deposits in the subiculum, expanding to interconnected brain regions such as retrosplenial granular cortex, thalamus, and mammillary bodies. Pathology more severe in females. | Spatial learning and memory deficit in the Barnes maze test in heterozygous females mice at 15 months. | Available through Annica Rönnbäck | Rönnbäck et al., 2011 | No | ||||
tg ArcSwe, APP-ArcSwe | C57BL/6J | APP | APP K670_M671delinsNL (Swedish), APP E693G (Arctic) | Transgene with human APP (isoform 695) containing both the Arctic (E693G) and Swedish (KM670/671NL) mutations under the murine Thy1 promoter. | APP: Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy | Strong intraneuronal Aβ aggregation starting at 1 month and increasing with age. Extracellular amyloid plaque at 5-6 months, most consistent in the cerebral cortex, hippocampus, and thalamus. Congophilic parenchymal plaques are predominant, but some mice show marked CAA, particularly in the thalamus. | Mild spatial learning deficits at 4-8 months in Morris water maze and impaired functioning in a passive avoidance test at 16 months. | Tg-ArcSwe have reduced body weight compared with nontransgenic littermates. | Available through Lars Nilsson | Lord et al., 2006 | Yes |
6 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-G-F Knock-in
Observed
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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. |
AppNL-G-F/MAPT double knock-in
Observed
-
Plaques at 8
Plaques observed at 2 months.
-
Gliosis at 16
Astrogliosis and microgliosis observed by 4 months.
-
Cognitive Impairment at 52
Deficits in the Y-maze test of working memory at 12 months of age.
Absent
-
Tangles at
No neurofibrillary tangles observed up to 24 months of age.
-
Neuronal Loss at
No neurodegeneration observed up to 24 months of age.
No Data
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
App, MAPT | APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic) | App: Knock-In; MAPT: Knock-In | Alzheimer's Disease | Amyloid plaques, plaque-associated neuritic dystrophy, and neuroinflammation, similar to AppNL-G-F. |
Deficits in the Y-maze test of working memory, similar to AppNL-G-F. |
AppSAA Knock-in
Observed
-
Plaques at 16
Amyloid plaques seen in AppSAA homozygous mice from 4 months of age and heterozygous mice at 16 months of age.
-
Gliosis at 16
Plaque-associated microgliosis observed by 4 months of age.
Absent
-
Tangles at
AT8-positive dystrophic neurites, but no neurofibrillary tangles, detected in AppSAA homozygous mice at 8 months of age.
No Data
-
Neuronal Loss at
No data.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
-
Cognitive Impairment at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
App | APP K670_M671delinsNL (Swedish), APP E693G (Arctic), APP T714I (Austrian) | App: Knock-In | Alzheimer's Disease | Homozygotes: Amyloid plaques and plaque-associated microgliosis from 4 months of age; cerebral amyloid angiopathy and dystrophic neurites from 8 months of age. Heterozygotes: Amyloid plaques at 16 months of age. |
Unknown. |
Arc48 (APPSw/Ind/Arc)
Observed
-
Plaques at 9
Parenchymal neuritic plaques by 2 months with prominent plaque deposition in the hippocampus by 3-4 months. Abundant mature thioflavin-S positive plaques with dystrophic neurites by 10-12 months (Cheng et al., 2007).
-
Gliosis at 13
Reactive astrocytosis at 3-4 months in the dentate gyrus as demonstrated by GFAP immunoreactivity (Cheng et al., 2007).
-
Cognitive Impairment at 13
At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but were impaired in the ability to use extramaze cues to navigate to the hidden platform (Cheng et al., 2007).
Absent
-
Tangles at
Absent.
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana), APP E693G (Arctic) | APP: Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy | Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20. |
At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform. |
ArcAβ
Observed
-
Plaques at 39
Between 9 and 15 months of age β-amyloid plaques became prominent. Plaques had a characteristic dense core morphology which differed from the cotton wool-like structure of plaques seen with the Swedish mutation alone (Knobloch et al., 2007).
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Changes in LTP/LTD at 15
LTP is severely impaired in slices from 3.5 and 7.5 month old mice. LTP and basal synaptic transmission were normal in slices from one month old mice (Knobloch et al., 2007).
-
Cognitive Impairment at 26
Cognitive impairment measured from the age of 6 months in the Morris water maze and Y-maze, as well as in active avoidance behavior (Knobloch et al., 2007).
Absent
-
Tangles at
Absent.
No Data
-
Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP E693G (Arctic) | APP: Transgenic | Alzheimer's Disease | At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma. | Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze. |
Tg-ArcSwe
Observed
-
Plaques at 22
Extracellular amyloid plaque deposition starts at around 5-6 months of age (Lord et al., 2006) and is most consistently present in the cerebral cortex, hippocampus, and thalamus (Lillehaug et al., 2013).
-
Gliosis at 26
Microgliosis and astrogliosis most prominent in the hippocampus, but also locally around deposits in the cerebral cortex and thalamus.
-
Cognitive Impairment at 17
Transgene-dependent spatial learning impairment in the Morris water maze (4-8 months) (Lord et al., 2009) and in an Intellicage-based Passive Avoidance test (16 months)(Codita et al., 2010).
Absent
-
Tangles at
Absent.
-
Neuronal Loss at
Absent.
No Data
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP E693G (Arctic) | APP: Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy | Strong intraneuronal Aβ aggregation starting at 1 month and increasing with age. Extracellular amyloid plaque at 5-6 months, most consistent in the cerebral cortex, hippocampus, and thalamus. Congophilic parenchymal plaques are predominant, but some mice show marked CAA, particularly in the thalamus. |
Mild spatial learning deficits at 4-8 months in Morris water maze and impaired functioning in a passive avoidance test at 16 months. |