Research Models
Selected Results
5 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 (5) |
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C57BL/6× DBA/2 | PSEN2 | PSEN2 N141I | Transgene containing human PSEN2 carrying the N141I mutation driven by the neuron-specific enolase (NSE) promoter. | PSEN2: Transgenic | Alzheimer's Disease | Not observed. | Behavioral deficits in the water maze at 12 months in mice expressing mutatnt as well as wild-type PSEN2, including longer escape latencies than wild-type mice, but no difference in swimming speed. | Expression of PSEN2 was higher in mice expressing mutant as well as wild-type PSEN2 compared to age-matched, non-transgenic mice. Alterations in levels of Aβ42, caspase-3 and Cox-2 proteins. | Unknown | Hwang et al., 2002 | No | ||||
B6.PS2APP, TG B6.PS2APP mice (line B6.152H) | Tg(Thy1-APPSwe,Prnp-PSEN2*N141I)152HLaoz | C57BL/6 | APP, PSEN2 | APP K670_M671delinsNL (Swedish), PSEN2 N141I | Coinjection of two transgenes into C57/Bl/6 zygotes: Human PSEN2 gene with the N141I mutation driven by the mouse prion protein promoter and human APP751 with the Swedish mutation driven by the Thy1.2 promoter. | APP: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Age-associated development of plaques: none at 3 months, overt Aβ deposition in the brain at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months. Aβ deposits in blood vessels were sporadic, mainly in large vessels. Cerebral amyloid deposits correlate with levels of the human APP transcript at 12 months. | Cognitive impariment detected by the Morris water maze at 8 and 12 months of age, but not at 3 months. | Decreased survival of newborn neurons in the dentate gyrus at about 4 months. Reduced endoplasmic reticulum Ca2+ and calcium dysregulation. A strong increase in LTP and post-tetanic potentiation (PTP) in hippocampal slices of 10 month old animals compared to wild-type mice. Decreased perfusion in the occipital cortex at all ages tested (10-17 months). | Available through Laurence Ozmen | Ozmen et al., 2009 | Yes | ||
PS2(N141I) x APPswe , hPS2(N141I) x hAPPswe | Tg(Thy1-APPSwe)71Jgr x Tg(Prnp-PSEN2*N141I)30Jgr | C57BL/6, DLB/2, crossed to C57BL/6 | APP, PSEN2 | APP K670_M671delinsNL (Swedish), PSEN2 N141I | Double transgenics created by crossing APPSwe mice (transgene containing the 751 isoform of human APP with the Swedish mutation driven by the Thy1.2 promoter) with PS2(N141I) mice (tansgene containing human PSEN2 with the N141I mutation driven by the mouse prion protein promoter). | APP: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution with time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei. The distribution and abundance of activated microglia and astrocytes correlate with Aβ deposition. | Mice develop age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze. | More insoluble Aβ40 and Aβ42 than age-matched APPSwe mice at 16-18 months. Loss of metabotropic glutamate receptors (mGlu2) in certain brain regions of aged mice as demonstrated by autoradiography. | Available through Laurence Ozmen | Richards et al., 2003 | Yes | ||
Prp-huPS2(N141I), PS2-N141I (line 30), hPS2mut | Tg(Prnp-PSEN2*N141I)30Jgr | Originally generated in a B6.D2 background, then crossed into C57BL/6J. | PSEN2 | PSEN2 N141I | Human PSEN2 gene with the N141I mutation driven by the mouse prion protein promoter. | PSEN2: Transgenic | Alzheimer's Disease | Unknown. | Unknown. | Ubiquitous expression of mutant transgene. Brain homogenate from 2 week-old mice had PSEN levels 1.8-2.2 fold higher than wild-type mice. Disrupted Ca2+ homeostasis, similar to that of double transgenic PS2APP mice, including a reduction in endoplasmic reticulum Ca2+ content in cultured neurons and a generally decreased response to metabotropic agonists. | Available through Laurence Ozmen | Richards et al., 2003 | No | ||
Triple transgenic, 3Tg | B6.D2-Tg(Thy1-APPSwe, Prp-PSEN2N141I, Thy1-TauP301L) | C57BL/6, DBA/2; backcrossed to C57BL/6 | APP, MAPT, PSEN2 | APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN2 N141I | PS2APP mice (line B6.152H) x tau mice (line B6.TauP301L). PS2APP were generated by co-injecting two transgenic constructs: human PSEN2 (N141I mutation) and human APP (Swedish mutation) driven by the mouse prion promoter and the mouse Thy1 promoter respectively. The transgenic TauP301L mouse (line pR5) expresses the human tau40 isoform driven by the Thy1.2 promoter. | APP: Transgenic; MAPT: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Phosphorylated tau accumulation in the subiculum and the CA1 region of the hippocampus at 4 months. Neurofibrillary tangles in these regions as well as the amygdala. Amyloid plaques. Dystrophic neurites and neuropil threads containing abnormally phosphorylated tau. No overt neuronal loss. | Impaired spatial learning in the Morris water maze at 4 months but impairment is not progressive between 4 and 12 months and appears to be independent of pathology. | Cortex-specific deficiencies in oxidative phosphorylation. Loss of mitochondrial membrane potential. Reduced cortical ATP. Increased superoxide anions and ROS compared to wild-type. No differences in APP expression, APP cleavage or Aβ accumulation compared to PS2APP. Levels of ptau422 increased in an age-dependent manner, but levels of ptau231 did not. | Available through Laurence Ozmen | Grueninger et al., 2010 | 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+.
PS2APP
Observed
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Plaques at 26
Age-associated development of plaques: none at 3 months, overt Aβ deposition at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months (Ozmen et al., 2009; Weidensteiner et al. 2009).
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Gliosis at 26
Gliosis at 6 months (personal communication, Laurence Ozmen).
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Changes in LTP/LTD at 43
A strong increase in LTP and post-tetanic potentiation induced by tetanic stimulation in hippocampal slices of 10 month-old animals compared to wild-type mice (Poirier et al., 2010).
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Cognitive Impairment at 35
Cognitive impairment is detected by the Morris water maze (probe trial 2) at 8 and 12 months of age, not at 3 months (personal communication Laurence Ozmen).
Absent
-
Tangles at
Absent.
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN2 | APP K670_M671delinsNL (Swedish), PSEN2 N141I | APP: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Age-associated development of plaques: none at 3 months, overt Aβ deposition in the brain at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months. Aβ deposits in blood vessels were sporadic, mainly in large vessels. Cerebral amyloid deposits correlate with levels of the human APP transcript at 12 months. |
Cognitive impariment detected by the Morris water maze at 8 and 12 months of age, but not at 3 months. |
PS2APP (PS2(N141I) x APPswe)
Observed
-
Plaques at 39
Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution over time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei (Richards et al., 2003).
-
Gliosis at 39
An inflammatory response indicated by the presence of activated microglia and astrocytes begins around 9 months. The onset, distribution, and abundance of activated microglia and astrocytes correlate with Aβ deposition.
-
Cognitive Impairment at 35
Age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze (Richards et al., 2003).
Absent
-
Tangles at
Absent.
-
Changes in LTP/LTD at
No difference in LTP in the dentate gyrus at 3 and 10 months compared to wild-type mice (Richards et al., 2003).
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN2 | APP K670_M671delinsNL (Swedish), PSEN2 N141I | APP: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution with time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei. The distribution and abundance of activated microglia and astrocytes correlate with Aβ deposition. |
Mice develop age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze. |
TauPS2APP
Observed
-
Plaques at 17
Rare amyloid plaques at 4 months, plaques become more abundant with age. By 8 months the number of amyloid plaques increases considerably in the subiculum and the CA1 region of the hippocampus (Grueninger et al., 2010).
-
Tangles at 70
Abnormally phosphorylated tau is detectable at 4 months in both TauPS2APP and tau single transgenic mice especially in the subiculum, amygdala, and the CA1 region of the hippocampus. Tau pathology increases with age with numerous tangle-like deposits in the hippocampus confirmed by Gallyas silver staining at 16 months (Grueninger et al., 2010).
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Cognitive Impairment at 17
Impairment is not age-associated and does not progress from age 4 months to 12 months (Grueninger et al., 2010).
Absent
-
Neuronal Loss at
No overt neuronal loss in the hippocampus at 16 months (Grueninger et al., 2010).
No Data
-
Gliosis at
Unknown.
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, MAPT, PSEN2 | APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN2 N141I | APP: Transgenic; MAPT: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Phosphorylated tau accumulation in the subiculum and the CA1 region of the hippocampus at 4 months. Neurofibrillary tangles in these regions as well as the amygdala. Amyloid plaques. Dystrophic neurites and neuropil threads containing abnormally phosphorylated tau. No overt neuronal loss. |
Impaired spatial learning in the Morris water maze at 4 months but impairment is not progressive between 4 and 12 months and appears to be independent of pathology. |