Research Models
Selected Results
24 Models
Name | Other Names | Strain Name | Genetic Background | Gene | Mutation | Modification Info | Modification | Disease | Neuropathology | Behavior/Cognition | Other Phenotype | Availability | Primary Paper | Visualization | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Mouse Models (23) |
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B6.Cg-Apoetm1.1(APOE*4)Adiuj Abca7em#2Adiuj Trem2em1Adiuj/J | C57BL/6J | Abca7, APOE, Trem2 | TREM2 R47H | CRISPR/Cas9 was used to introduce the rs3752246 SNP mutation (p.A1527G) into the Abca7 gene of double mutant mice with a humanized APOE4 gene and the R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Laboratory Stock# 028709). | Abca7: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Laboratory, Stock# 030283. Cryopreserved. | The Jackson Laboratory | Yes | ||||
B6.Cg-Apoetm1.1(APOE*4)Adiuj Abca7em#1Adiuj Trem2em1Adiuj/J | C57BL/6J | Abca7, APOE, Trem2 | TREM2 R47H | CRISPR/cas9 was used to generate a knock-out mutation of the Abca7 gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Laboratory Stock# 028709). | Abca7: Knock-Out; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Laboratory, Stock# 030320. Cryopreserved. | The Jackson Laboratory | Yes | ||||
B6.Cg-Apoetm1.1(APOE*4)Adiuj Appem2Adiuj Trem2em1Adiuj/J | C57BL/6J | APOE, App, Trem2 | TREM2 R47H | CRISPR/Cas9 was used to introduce a 94-bp deletion in exon 14 (APP695 numbering) of the App gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (The Jackson Laboratory Stock# 028709). | APOE: Knock-In; App: Knock-Out; Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Laboratory, Stock# 031722. Cryopreserved. | The Jackson Laboratory | Yes | ||||
APOE4/Trem2*R47H/Ceacam1 knock-out | B6.Cg-Apoetm1.1(APOE*4)Adiuj Ceacam1em#1Adiuj Trem2em1Adiuj/J | C57BL/6J | APOE, Ceacam1, Trem2 | TREM2 R47H | CRISPR/cas9 was used to generate a knock-out mutation of the Ceacam1 gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Labortory Stock# 028709). | APOE: Knock-In; Ceacam1: Knock-Out; Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Laboratory, Stock# 030673. Cryopreserved. | The Jackson Laboratory | Yes | |||
B6(SJL)-Apoetm1.1(APOE*4)Adiuj Clasp2em1Adiuj Trem2em1Adiuj/J | C57BL/6J | Clasp2, APOE, Trem2 | TREM2 R47H | CRISPR/cas9 was used to generate a knock-in L163P mutation of the Clasp2 gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene. | Clasp2: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Laboratory, Stock# 031944. Cryopreserved. | The Jackson Laboratory | Yes | ||||
B6.Cg-Apoetm1.1(APOE*4)Adiuj Appem#1Adiuj Trem2em1Adiuj/J | C57BL/6J | APOE, APP, Trem2 | TREM2 R47H | CRISPR/Cas9 was used to introduce the G601R, F606Y, and R609H (APP695 numbering) point mutations into the App gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, Jackson Lab Stock# 028709). | APOE: Knock-In; APP: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Laboratory, Stock# 030670. Live. | The Jackson Laboratory | Yes | ||||
B6(SJL)-Cr2tm1(CR2,CR1)How Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J | C57BL/6J | Cr2, CR1, CR2, APOE, Trem2 | TREM2 R47H | This mutant line was generated by crossing APOE4/Trem2*R47H mice to mice in which the endogenous Cr2 gene was replaced with human CR1 and CR2 (The Jackson Laboratory Stock# 027713). | Cr2: Knock-Out; CR1: Knock-In; CR2: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Laboratory, Stock# 031668. Cryopreserved. | The Jackson Laboratory | Yes | ||||
B6.Cg-Apoetm1.1(APOE*4)Adiuj Il1rapem#1Adiuj Trem2em1Adiuj/J | C57BL/6J | APOE, Il1rap, Trem2 | TREM2 R47H | CRISPR/cas9 was used to generate a knock-out mutation of the Il1rap gene of double mutant mice with a humanized APOE4 gene and the R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Laboratory Stock# 028709). | APOE: Knock-In; Il1rap: Knock-Out; Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Laboratory, Stock# 030304. Cryopreserved. | The Jackson Laboratory | Yes | ||||
B6(SJL)-Kif21bem1Adiuj Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J | C57BL/6J | Kif21b, APOE, Trem2 | TREM2 R47H | CRISPR/cas9 was used to generate a knock-in T82T mutation of the Kif21b gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene. | Kif21b: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Laboratory, Stock# 031938. Cryopreserved. | The Jackson Laboratory | Yes | ||||
B6(SJL)-Mthfrem1Adiuj Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J | C57BL/6J | Mthfr, APOE, Trem2 | TREM2 R47H | CRISPR/Cas9 was used to introduce the A262V mutation into the Mthfr gene of APOE4/Trem2*R47H mice—double mutant mice with a humanized APOE4 gene and the R47H point mutation knocked into the mouse Trem2 gene. | Mthfr: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Laboratory, Stock# 030922. Cryopreserved. | The Jackson Laboratory | Yes | ||||
B6.Cg-Apoetm1.1(APOE*4)Adiuj Plcg2em2Adiuj Trem2em1Adiuj/J | C57BL/6J | APOE, Plcg2, Trem2 | TREM2 R47H | CRISPR/Cas9 was used to introduce the p.M28L mutation (methionine to leucine at position 28) into the Plcg2 gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Laboratory Stock# 028709). | APOE: Knock-In; Plcg2: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Laboratory, Stock# 030674. Cryopreserved. | The Jackson Laboratory | Yes | ||||
PS19-T2R47H, PS19-TREM2R47H | C57BL/6 | MAPT, TREM2, Trem2 | MAPT P301S, TREM2 R47H | These mice carry a human MAPT transgene with the P301S mutation linked to frontotemporal dementia and a BAC transgene encoding the R47H variant of human TREM2, on a Trem2 knockout background. | MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out | Alzheimer's Disease, Frontotemporal Dementia | Decreased brain atrophy, microgliosis, astrogliosis, and synapse loss, compared with PS19 mice carrying the common variant of TREM2. | Not known. | Decreased expression of pro-inflammatory cytokines and DAM (disease-associated microglia) genes, compared with PS19 mice carrying the common variant of TREM2. | PS19 mice are available from The Jackson Laboratory (Stock# 008169). TREM2 mice are available through Marco Colonna. | Gratuze et al., 2020 | Yes | |||
B6(SJL)-Apoetm1.1(APOE*4)Adiuj Snx1em1Adiuj Trem2em1Adiuj/J | C57BL/6J | Snx1, APOE, Trem2 | TREM2 R47H | CRISPR/cas9 was used to generate a D465N mutation in the Snx1 gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene. | Snx1: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Laboratory, Stock# 031942. Cryopreserved. | The Jackson Laboratory | Yes | ||||
B6(SJL)-Apoetm1.1(APOE*4)Adiuj Sorl1em1Adiuj Trem2em1Adiuj/J | C57BL/6J | Sorl1, APOE, Trem2 | TREM2 R47H, SORL1 A528T (SNP 13), APOE C130R (ApoE4) | CRISPR/cas9 was used to generate a knock-in A528T mutation of the Sorl1 gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene. | Sorl1: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Laboratory, Stock# 031940. Cryopreserved. | The Jackson Laboratory | Yes | ||||
R47H+mTrem2−/−, R47H-KO, TREM2R47H | C57BL/6 × CBA, backcrossed for at least four generations to C57BL/6. | TREM2, Trem2 | TREM2 R47H | BAC transgenic mice carrying human TREM2 (R47H variant), TREML1, and TREML2 were backcrossed to Trem2 knockout mice to yield mice that express the R47H variant of human TREM2 in the absence of mouse Trem2. | TREM2: Transgenic; Trem2: Knock-Out | Alzheimer's Disease | Unknown. | Unknown. | TREM2 mice are available through Marco Colonna. | Song et al., 2018 | Yes | ||||
R47H+mTrem2−/−5XFAD | C57BL/6 X CBA, back-crossed for at least 4 generations to C57BL/6 | Trem2, TREM2, APP, PSEN1 | TREM2 R47H, APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | BAC-transgenic mice carrying the human TREM2 (R47H variant), TREML1, and TREML2 were back-crossed to Trem2 KO mice (Colonna) to yield mice that express the R47H variant of human TREM2 in the absence of mouse Trem2. These mice were then crossed with 5XFAD mice. | Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Lower density of activated microglia surrounding amyloid plaques in 5XFAD mice expressing the R47H variant of human TREM2 compared with those expressing the common variant. | No data. | TREM2 mice: available through Marco Colonna; 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live | Song et al., 2018 | Yes | ||||
Trem2*R47HHSS | B6.Cg-Trem2em4Adiuj/J | C57BL/6J | Trem2 | TREM2 R47H | CRISPR/Cas9 was used to edit the mouse Trem2 locus in the Trem2 R47H KI (JAX) model (JAX #27918), “humanizing” the cryptic splice acceptor site in exon 2 in the context of the existing R47H point mutation and two silent mutations. | Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | Register interest at The Jackson Laboratory, Stock No. 033781. | The Jackson Laboratory | Yes | |||
R47H ki | Trem2em2 Bwef | C57BL/6N | Trem2 | TREM2 R47H | CRISPR/Cas9 was used to introduce an R47H point mutation (arginine CGC > histidine CAC) and three silent mutations (glycine: GGG > GGT; arginine: AGA > CGA; lysine: AAG > AAA) into the mouse Trem2 gene. The silent mutations were added to aid in genotyping and increase the efficiency of gene editing. | Trem2: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | R47H KI mice exhibit a gene-dose-dependent reduction in expression of Trem2, due to aberrant splicing of the mutant allele. | Available through Christian Haass. | Xiang et al., 2018 | Yes | ||
MODEL-AD R47H, Trem2*R47HCSS (for cryptic splice site), B6.Trem2*R47H | C57BL/6J-Trem2em1Adiuj/J | C57BL/6J | Trem2 | TREM2 R47H | CRISPR/Cas9 was used to introduce an R47H missense mutation and two silent mutations—to aid in genotyping and increase gene-editing efficiency—into the mouse Trem2 gene. | Trem2: Knock-In | Alzheimer's Disease | No neuron loss, amyloid plaques, or neurofibrillary tangles were observed in mice up to 24 months of age. | Locomotor activity, motor coordination, and working memory similar to wild-type at 2 and 12 months of age. | Compared with wild-type mice: age-, sex-, and region-dependent differences in glucose uptake and cerebral blood flow; increased mortality of females at 24 months of age; downregulation of genes related to immune function, and degradation of biological material in aged mice. | The Jackson Lab:Stock# 027918; Cryorecovery. | Kotredes et al., 2021, Tran et al., 2023 | Yes | ||
Trem2+/R47H | C57BL6/J | Trem2 | TREM2 R47H | CRISPR/Cas9 was used to introduce the R47H variant into the endogenous mouse Trem2 gene. | Trem2: Knock-In | Alzheimer's Disease | No 6E10- or Thioflavin S-positive amyloid plaques were observed at 4 months of age. | Unknown. | Approximate 40 percent decrease in levels of Trem2 mRNA in cortices of Trem2+/R47H mice compared with Trem2+/+ mice. | Available through Gary Landreth or Bruce Lamb. | Cheng-Hathaway et al., 2018 | 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 | |||
APOE4/Trem2*R47H, APOE*4/Trem2*R47H, APOE4.Trem2*R47H, LOAD1 | B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J | C57BL/6J | APOE, Trem2 | TREM2 R47H, APOE C130R (ApoE4) | This double-mutant line was generated by crossing APOE4 KI mice (Jackson Lab Stock# 027894), which carry a humanized APOE4 gene, to Trem2 R47H KI mice (Jackson Lab Stock # 027918), which have an R47H missense mutation knocked into the mouse Trem2 gene. | APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | No neuron loss, amyloid plaques, neurofibrillary tangles, vascular leakage, myelin loss, or reactive microglia in mice up to 24 months of age. | Age-related changes in locomotor activity, motor coordination, and working memory, but no genotype-dependent differences through 24 months of age, compared with wild-type mice. | Age-, sex-, and region-dependent differences in glucose uptake and cerebral blood flow, compared with wild-type mice. Increased mortality at 24 months of age. Down-regulation of genes related to immune function and degradation of biological material in aged mice. | The Jackson Lab:Stock# 028709; Live | Kotredes et al., 2021 | Yes | ||
Trem2*R47HNSS | B6(SJL)-Trem2em1Aduci/J | C57BL/6J | Trem2 | TREM2 R47H | CRISPR/Cas9 was used to edit the mouse Trem2 gene, introducing the R47H point mutation and 10 silent mutations in exon 2. | Trem2: Knock-In | Alzheimer's Disease | Changes in microglial morphology at 4 months but not 12 months, compared with wild-type. | Unknown. | Age-dependent synaptic deficits and age-dependent differences in gene expression, compared with wild-type mice. When crossed with 5xFAD mice, blunted inflammatory responses at 4 months, but exaggerated responses at 12 months. | Available from The Jackson Laboratory, Stock No. 034036. | Tran et al., 2023, The Jackson Laboratory | Yes | ||
Rat Models (1) |
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Trem2R47H | Long-Evans | Trem2, App | TREM2 R47H | Rats carry the R47H mutation in the endogenous Trem2 gene and a humanized Aβ sequence within the endogenous App gene. | Trem2: Knock-In; App: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | Available through Luciano D'Adamio. | Tambini and D'Adamio, 2020 | Yes |
24 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+.
Abca7*A1527G/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Abca7, APOE, Trem2 | TREM2 R47H | Abca7: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Abca7 KO/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Abca7, APOE, Trem2 | TREM2 R47H | Abca7: Knock-Out; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
App KO/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE, App, Trem2 | TREM2 R47H | APOE: Knock-In; App: Knock-Out; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Ceacam1 KO/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE, Ceacam1, Trem2 | TREM2 R47H | APOE: Knock-In; Ceacam1: Knock-Out; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Clasp2*L163P/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Clasp2, APOE, Trem2 | TREM2 R47H | Clasp2: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
hAbeta/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE, APP, Trem2 | TREM2 R47H | APOE: Knock-In; APP: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
hCR1 KI on APOE4/Trem2
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Cr2, CR1, CR2, APOE, Trem2 | TREM2 R47H | Cr2: Knock-Out; CR1: Knock-In; CR2: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Il1rap KO/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE, Il1rap, Trem2 | TREM2 R47H | APOE: Knock-In; Il1rap: Knock-Out; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Kif21b*T82T/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Kif21b, APOE, Trem2 | TREM2 R47H | Kif21b: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Mthfr*C677T/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Mthfr, APOE, Trem2 | TREM2 R47H | Mthfr: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Plcg2*M28L/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE, Plcg2, Trem2 | TREM2 R47H | APOE: Knock-In; Plcg2: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
PS19 with humanized TREM2 (R47H)
Observed
-
Tangles at 36
Tangles revealed using antibody PG5 at 9 months.
Absent
No Data
-
Plaques at
No data.
-
Neuronal Loss at
No data relative to wild-type mice, but at 9 months of age, the volumes of the hippocampus and entorhinal/piriform cortex are larger, and the granule cell layer of the dentate gyrus and pyramidal cell layer of the piriform cortex are thicker, in PS19-TREM2R47H mice, compared with PS19 mice carrying the common variant of human TREM2.
-
Gliosis at
At 9 months of age, decreased expression of markers of astroglial and microglial reactivity, compared with PS19 mice carrying the common variant of TREM2, but no data relative to wild-type mice.
-
Synaptic Loss at
At 9 months of age, more synapses and fewer dystrophic synapses, compared with PS19 mice carrying the common variant of TREM2, but no data relative to wild-type mice.
-
Changes in LTP/LTD at
No data.
-
Cognitive Impairment at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT, TREM2, Trem2 | MAPT P301S, TREM2 R47H | MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out | Alzheimer's Disease, Frontotemporal Dementia | Decreased brain atrophy, microgliosis, astrogliosis, and synapse loss, compared with PS19 mice carrying the common variant of TREM2. |
Not known. |
Snx1*D465N/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
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 |
---|---|---|---|---|---|
Snx1, APOE, Trem2 | TREM2 R47H | Snx1: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Sorl1*A528T/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis at
No data.
-
Synaptic 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 |
---|---|---|---|---|---|
Sorl1, APOE, Trem2 | TREM2 R47H, SORL1 A528T (SNP 13), APOE C130R (ApoE4) | Sorl1: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
TREM2, humanized (R47H)
Observed
Absent
-
Gliosis at
Expression of DAM (disease-associated microglia) genes is low at 8.5 months, suggesting that microglia are in a resting or homeostatic state.
No Data
-
Plaques at
No data.
-
Tangles at
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 |
---|---|---|---|---|---|
TREM2, Trem2 | TREM2 R47H | TREM2: Transgenic; Trem2: Knock-Out | Alzheimer's Disease | Unknown. |
Unknown. |
TREM2, humanized (R47H) X 5XFAD
Observed
-
Plaques at 34
Plaques observed in 8.5-month-old mice, the only age reported thus far.
-
Gliosis at 34
Microgliosis observed in 8.5-month-old mice, the only age reported thus far. Fewer plaque-associated microglia in mice expressing the R47H variant, compared with the common variant of human TREM2.
Absent
No Data
-
Tangles at
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 |
---|---|---|---|---|---|
Trem2, TREM2, APP, PSEN1 | TREM2 R47H, APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Lower density of activated microglia surrounding amyloid plaques in 5XFAD mice expressing the R47H variant of human TREM2 compared with those expressing the common variant. |
No data. |
Trem2*R47H(HSS)
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 | TREM2 R47H | Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Trem2 R47H KI (Haass)
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 | TREM2 R47H | Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Trem2 R47H KI (JAX)
Observed
Absent
-
Plaques at
Not observed in cortex or hippocampus up to 24 months of age.
-
Tangles at
Not observed in cortex or hippocampus up to 24 months of age.
-
Neuronal Loss at
Not observed in cortex or hippocampus up to 24 months of age.
-
Cognitive Impairment at
Locomotor activity, motor coordination, and working memory similar to wild-type at 2 and 12 months of age.
No Data
-
Gliosis at
No data.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
Trem2 | TREM2 R47H | Trem2: Knock-In | Alzheimer's Disease | No neuron loss, amyloid plaques, or neurofibrillary tangles were observed in mice up to 24 months of age. |
Locomotor activity, motor coordination, and working memory similar to wild-type at 2 and 12 months of age. |
Trem2 R47H KI (Lamb/Landreth)
Observed
Absent
-
Plaques at
No 6E10- or Thioflavin S-positive amyloid plaques were observed at 4 months of age.
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 | TREM2 R47H | Trem2: Knock-In | Alzheimer's Disease | No 6E10- or Thioflavin S-positive amyloid plaques were observed at 4 months of age. |
Unknown. |
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.
-
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.
-
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 |
---|---|---|---|---|---|
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. |
Trem2 R47H KI x APOE4
Observed
Absent
-
Plaques at
Not observed in cortex or hippocampus up to 24 months of age.
-
Tangles at
Not observed in cortex or hippocampus up to 24 months of age.
-
Neuronal Loss at
Not observed in cortex or hippocampus up to 24 months of age.
-
Gliosis at
Microgliosis not observed in cortex or hippocampus up to 24 months of age.
-
Cognitive Impairment at
Age-related changes in locomotor activity, motor coordination, and working memory, but no genotype-dependent differences through 24 months of age, compared with wild-type mice.
No Data
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APOE, Trem2 | TREM2 R47H, APOE C130R (ApoE4) | APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | No neuron loss, amyloid plaques, neurofibrillary tangles, vascular leakage, myelin loss, or reactive microglia in mice up to 24 months of age. |
Age-related changes in locomotor activity, motor coordination, and working memory, but no genotype-dependent differences through 24 months of age, compared with wild-type mice. |
Trem2 R47H knock-in
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 | TREM2 R47H | Trem2: Knock-In; App: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Trem2*R47H(NSS)
Observed
-
Synaptic Loss at 50
Synapse loss, assessed by co-localization of the pre-synaptic marker bassoon and postsynaptic marker PSD95, by 12 months.
-
Changes in LTP/LTD at 52
Impaired basal synaptic transmission and LTP, by 12 months.
Absent
-
Plaques at
Not observed.
-
Tangles at
Not observed.
-
Gliosis at
Similar numbers of Iba1-immunoreactive microglia in Trem2*R47HNSS and wild-type hippocampi and cortices, but differences in microglial morphology at 4 months that are gone by 12 months.
No Data
-
Neuronal Loss at
No data.
-
Cognitive Impairment at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
Trem2 | TREM2 R47H | Trem2: Knock-In | Alzheimer's Disease | Changes in microglial morphology at 4 months but not 12 months, compared with wild-type. |
Unknown. |