Research Models
Selected Results
3 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 (3) |
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APPPS1-21, APP/PS1 | B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr | C57BL/6J | APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 L166P | Human transgenes APP KM670/671NL and PSEN1 L166P, both under the control of the Thy1 promoter. Integration site is on lower arm of chromosome 2 between 40 and 60 cm. | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaque deposition starts at approximately 6 weeks in the neocortex. Amyloid deposits in the hippocampus appear at 3-4 months, and in the striatum, thalamus and brainstem at 4-5 months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen. | Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months. Impaired reversal learning of a food-rewarded four-arm spatial maze task at 8 months. | Aβ42 concentration in CSF decreases with age, with a 50% reduction by 6 months and an 80% reduction by 18 months. Aβ40 concentration also decreases, but less robustly (45% by 18 months). CSF concentration of total tau increases, starting at 6 months, and reaches a 5-fold increase by 18 months. | Available through Mathias Jucker | Radde et al., 2006 | Yes | ||
APPPS1;Trem2-/- | TREM2tm1(KOMP)Vlcg; B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr | C57BL/6 | Trem2, APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 L166P | Trem2-/-: The entire coding region of the Trem2 gene was replaced by Velocigene cassette ZEN-Ub1 (lacZ-p(A)-loxP-hUbCpro-neor-p(A)-LoxP). APPPS1: Mice express human APP with the Swedish (K670M/N671L) mutations and human PSEN1 with the L166P mutation, both under control of the Thy1 promoter. | Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Reduced plaque burden at early stages of plaque deposition but increased plaque burden at later stages, fewer plaque-associated myeloid cells and astrocytes, less phospho-tau in plaque-associated dystrophic neurites, compared with APPPS1. | No data. | APPPS1 available through Mathias Jucker; Trem2 KO available through UC Davis KOMP Repository, Project VG10093, cryo-recovery or sperm | Jay et al., 2015, Jay et al., 2017 | Yes | |||
APPPS1-21;Trem2+/R47H | C57BL6/J | Trem2, APP, PSEN1 | TREM2 R47H, APP K670_M671delinsNL (Swedish), PSEN1 L166P | To create Trem2+/R47H mice, CRISPR/Cas9 was used to introduce the R47H variant into the endogenous mouse Trem2 gene. APPPS1-21 mice express human APP with the Swedish (K670M/N671L) mutations and human PSEN1 with the L166P mutation, both under control of the Thy1 promoter. | Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Reduction in the number and burden of fibrillar amyloid plaques in the hippocampus, fewer plaque-associated myeloid cells, and worse plaque-associated neuritic dystrophy, compared with APPPS1-21 mice homozygous for wild-type Trem2. | Unknown. | Levels of Trem2 transcripts were reduced in APPPS1-21;Trem2+/R47H compared with APPPS1-21;Trem2+/+ and were similar to those in APPPS1-21 mice haploinsufficient for Trem2. | Trem2+/R47H available through Gary Landreth or Bruce Lamb; APPPS1-21 available through Mathias Jucker. | Cheng-Hathaway et al., 2018 | 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+.
APPPS1
Observed
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Plaques at 6
Aβ deposition begins at 6 weeks of age in the cortex and 3-4 months of age in the hippocampus (Radde et al., 2006).
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Neuronal Loss at 74
Global neuron loss is not observed, but modest neuron loss was found in the granule cell layer of the dentate gyrus and other subregions with high neuronal density in 17-month old animals (Rupp et al., 2011).
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Gliosis at 6
Activated microglia around Aβ deposits at 6 weeks as well as increased astrogliosis (Radde et al., 2006). Levels of CCL2 and TNFα increase at later ages (Lee et al., 2010).
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Synaptic Loss at 10
Dendritic spine loss around plaques reported to begin approximately 4 weeks after plaque formation and continue for several months (Bittner et al., 2012).
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Changes in LTP/LTD at 35
Hippocampal CA1 LTP normal at 4.5 months of age, but impaired at 8 and 15 months of age (Gengler et al., 2010).
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Cognitive Impairment at 30
Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months (Serneels et al., 2009). Impaired reversal learning of a food-rewarded four-arm spatial maze task observed at 8 months (Radde et al., 2006).
Absent
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Tangles at
Phosphorylated tau-positive neuritic processes around plaques have been observed, but no mature tangles (Radde et al., 2006).
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
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APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 L166P | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaque deposition starts at approximately 6 weeks in the neocortex. Amyloid deposits in the hippocampus appear at 3-4 months, and in the striatum, thalamus and brainstem at 4-5 months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen.
|
Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months. Impaired reversal learning of a food-rewarded four-arm spatial maze task at 8 months. |
Trem2 KO (KOMP) x APPPS1
Observed
-
Plaques at 9
Plaques are observed by 2 months.
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Gliosis at 9
Gliosis is observed by 2 months.
Absent
No Data
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Tangles at
No data.
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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 |
---|---|---|---|---|---|
Trem2, APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 L166P | Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Reduced plaque burden at early stages of plaque deposition but increased plaque burden at later stages, fewer plaque-associated myeloid cells and astrocytes, less phospho-tau in plaque-associated dystrophic neurites, compared with APPPS1. |
No data. |
Trem2 R47H KI (Lamb/Landreth) X APPPS1-21
Observed
-
Plaques at 16
Reduction in the number and burden of fibrillar amyloid plaques in the hippocampus, compared with APPPS1-21 mice homozygous for wild-type Trem2.
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Gliosis at 16
Fewer plaque-associated myeloid cells in APPPS1-21;Trem2+/R47H, compared with APPPS1-21 mice homozygous for wild-type Trem2.
Absent
-
Tangles at
Tangles were not observed at 4 months of age, but hyperphosphorylated tau was detected in dystrophic neurites surrounding plaques.
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Neuronal Loss at
No differences in neuron number in cotical layer V in APPPS1-21;Trem2+/R47H mice relative to APPPS1-21 mice homozygous for wild-type Trem2, at 4 months of age.
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 |
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Trem2, APP, PSEN1 | TREM2 R47H, APP K670_M671delinsNL (Swedish), PSEN1 L166P | Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Reduction in the number and burden of fibrillar amyloid plaques in the hippocampus, fewer plaque-associated myeloid cells, and worse plaque-associated neuritic dystrophy, compared with APPPS1-21 mice homozygous for wild-type Trem2. |
Unknown. |