Research Models
Selected Results
4 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 (4) |
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APP-Dutch, Tg-APP(Dutch), APP E693Q, APP Dutch | C57BL/6J-Tg(Thy1-APPDutch)#Jckr | C57BL/6J | APP | APP E693Q (Dutch) | Transgenic mice with human APP751 bearing the E693Q mutation under the murine Thy1 promoter. | APP: Transgenic | Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease | Increased Aβ40/42 ratio. Extensive vascular Aβ deposition starting at 22-24 months appearing first in leptomeningeal vessels followed by cortical vessels, leading to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. Parenchymal amyloid plaques are not observed. | Unknown. | Available through Mathias Jucker | Herzig et al., 2004 | Yes | |||
APP KI, line ADF | Apptm1Sud/J | Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl<+>; C57BL/6 and maintained on a mixed background | APP | APP K670_M671delinsNL (Swedish), APP V717I (London), APP E693Q (Dutch) | Knock-in of wild-type mouse APP exon 16 (truncated after residue KM), FLAG tag (2 repeats), a stop codon, a poly A signal region from the human growth hormone gene and an additional copy of exon 16 carrying the Swedish mutation and a modified exon 17 with the London and Dutch mutations. | APP: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Lab: Stock# 008390; Cryopreserved | The Jackson Laboratory | No | |||
APPSwDI/NOS2 bigenic mice, APPSDI/NOS2KO, CVN | B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/Mmjax | C57BL/6J; C57BL/6N | APP, NOS2 | APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) | APPSwDI x NOS2 knockout animals. APPSwDI transgene expresses APP (isoform 770) with Swedish, Dutch, and Iowa mutations under the control of the mouse Thy1 promoter. NOS2 was disrupted by homologous recombination. The calmodulin binding domain of NOS2 was replaced by the neomycin resistance gene and the reading frame disrupted. | APP: Transgenic; NOS2: Knock-Out | Alzheimer's Disease | Plaques especially in the thalamus and subiculum. Aggregated, hyperphosphorylated tau tangles. Neuronal loss especially of NPY neurons in the hippocampus and subiculum. More severe pathology than Tg-SwDI alone. | Severe learning and memory deficits. Impaired spatial memory compared to Tg-SwDI as measured by the radial arm maze and the Barnes maze at 52-56 weeks. | Decreased neuropeptide Y staining throughout the hippocampus, particularly in the CA3 region and subiculum. | The Jackson Lab; available through the JAX MMRRC Stock# 034849; Cryopreserved. Charles River: CVN mouse | Colton et al., 2008, Wilcock et al., 2008 | Yes | ||
APP-Swedish,Dutch,Iowa, APPSwDI | C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax | C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) | Transgenic mice with 2.1 kb of the human APP gene (isoform 770) with the Swedish (K670N/M671L), Dutch (E693Q) and Iowa (D694N) mutations under the control of the mouse Thy1 promoter. | APP: Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type | Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Fibrillar Aβ in micovessels around 6 months. Diffuse plaque-like deposits around 3 months in the subiculum, hippocampus and cortex. Aβ deposits throughout the forebrain by 12 months. | Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months. Beginning at 3 months transgenic mice took longer to find the escape hole. No difference in mobility, strength or coordination. | The Jackson Lab; available through the JAX MMRRC Stock# 034843; Live | Davis et al., 2004 | 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+.
APPDutch
Observed
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Gliosis at 126
Microgliosis develops after the onset of CAA pathology and is prominent in areas adjacent to amyloid-laden vessels. There is also widespread activation of astrocytes in neocortical regions affected by CAA. These changes have been reported at 29 months of age, although the actual onset of gliosis may occur earlier than has been examined.
Absent
-
Plaques at
No plaques are observed, but CAA develops at 22-24 months.
-
Tangles at
Absent.
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
-
Cognitive Impairment at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP E693Q (Dutch) | APP: Transgenic | Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease | Increased Aβ40/42 ratio. Extensive vascular Aβ deposition starting at 22-24 months appearing first in leptomeningeal vessels followed by cortical vessels, leading to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. Parenchymal amyloid plaques are not observed. |
Unknown. |
APPSwDI x NOS2 Knock-out
Observed
-
Plaques at 49
Aβ deposits by 52 weeks. Particularly dense Aβ immunoreactivity in the subiculum and thalamus, including in the cerebral microvessels (Wilcock et al., 2008).
-
Tangles at 49
Extensive tau pathology by 52 weeks, including intraneuronal aggregates of hyperphosphorylated tau. Increased phosphorylated tau in bigenic mice compared to APPSwDI mice (Wilcock et al., 2008).
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Neuronal Loss at 52
Significant neuron loss by 52 weeks in the hippocampus and subiculum, especially of neuropeptide Y neurons. Numerous Fluoro-Jade C+ neurons: 30% loss in the hippocampus, 35% loss in the subiculum (Wilcock et al., 2008).
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Cognitive Impairment at 53
Impairments in spatial memory by 52-56 weeks as measured by the radial arm maze and the Barnes maze. Bigenic mice more impaired than APPSwDI (Wilcock et al., 2008).
Absent
No Data
-
Gliosis at
Unknown.
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, NOS2 | APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) | APP: Transgenic; NOS2: Knock-Out | Alzheimer's Disease | Plaques especially in the thalamus and subiculum. Aggregated, hyperphosphorylated tau tangles. Neuronal loss especially of NPY neurons in the hippocampus and subiculum. More severe pathology than Tg-SwDI alone. |
Severe learning and memory deficits. Impaired spatial memory compared to Tg-SwDI as measured by the radial arm maze and the Barnes maze at 52-56 weeks. |
Tg-SwDI (APP-Swedish,Dutch,Iowa)
Observed
-
Plaques at 13
Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Amyloid-β deposits in the subiculum, hippocampus, and cortex at ~3 months. By ~6 months deposits become more numerous and appear in the olfactory bulb and thalamic region as well, with deposits throughout most of the forebrain by 12 months (Davis et al., 2004).
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Gliosis at 26
Pronounced increase in the number of GFAP-positive astrocytes and activated microglia with age (6-24 months) especially in the thalamus and subiculum and to a lesser extent in the cortex (Miao et al., 2005).
-
Cognitive Impairment at 13
Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months; beginning at 3 months took longer to find the escape hole. No difference in mobility, strength or coordination (Xu et al., 2007).
Absent
-
Tangles at
Absent.
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) | APP: Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type | Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Fibrillar Aβ in micovessels around 6 months. Diffuse plaque-like deposits around 3 months in the subiculum, hippocampus and cortex. Aβ deposits throughout the forebrain by 12 months. |
Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months. Beginning at 3 months transgenic mice took longer to find the escape hole. No difference in mobility, strength or coordination. |