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Name Other Names Strain Name Genetic Background Gene Mutation Modification Info Modification Disease Neuropathology Behavior/Cognition Other Phenotype Availability Primary Paper Visualization
Mouse Models (18)
<p>-</p>, <p>E2F</p> C57BL/6J APOE The coding region of the mouse Apoe gene, from the translation initiation codon in exon 2 to the termination codon in exon 4, was replaced with the corresponding human APOE (ε2 allele) sequence, flanked by loxP sites. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Available through a material transfer agreement with the Cure Alzheimer’s Fund. Huynh et al., 2019 Yes
<p>-</p>, <p>E3F</p> C57BL/6J APOE The coding region of the mouse Apoe gene, from the translation initiation codon in exon 2 to the termination codon in exon 4, was replaced with the corresponding human APOE (ε3 allele) sequence, flanked by loxP sites. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Available through a material transfer agreement with the Cure Alzheimer’s Fund. Huynh et al., 2019 Yes
<p>-</p>, <p>APOE3 Humanized Knock-in</p> B6.129P2-Apoetm2(APOE*3)Mae N8 129 x C57BL/6; back-crossed to C57BL/6 APOE Targeted replacement of the endogenous mouse APOE gene with the human APOE3 allele. Targeting vector contained exons 2-4 of human APOE3. APOE: Knock-In Alzheimer's Disease, Multiple Conditions None reported. APOE3 was considered the neutral allele against which the other human APOE genotypes were compared in most studies of neurological phenotypes in Targeted Replacement mice. Data comparing Targeted Replacement mice to wild-type mice are limited. Findings are mixed, with some studies reporting that APOE genotype—in some cases, interacting with sex or age—affects performance in behavioral assays. On a standard diet, homozygous mice have normal cholesterol and triglyceride levels, but are more susceptible than wild-type animals to diet-induced atherosclerosis. Data comparing neurological phenotypes in Targeted Replacement mice to wild-type mice are sparse, but APOE3 mice resemble wild-type mice with respect to aspects of hippocampal anatomy and physiology, including LTP and neurogenesis. Taconic: Stock# 1548-F and 1548-M Sullivan et al., 1997 No
<p>-</p>, <p>E4F</p> C57BL/6J APOE The coding region of the mouse Apoe gene, from the translation initiation codon in exon 2 to the termination codon in exon 4, was replaced with the corresponding human APOE (ε4 allele) sequence, flanked by loxP sites. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Available through a material transfer agreement with the Cure Alzheimer’s Fund. Huynh et al., 2019 Yes
<p>-</p>, <p>APPPS1-21</p>, <p>APP/PS1</p> 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
<p>-</p>, <p>APPswe/PSEN1dE9/MAPT</p>, <p>APPswe/PSEN1dE9/CaMKIIa-tTa/TRE-Tg21221</p> B6.C3 x B6.129 x FVB APP, PSEN1, MAPT APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 APPswe/PSEN1dE9 mice were crossed with B6.129-Tg(CK-tTa) mice where the CaMKIIa promotor drives expression of tetracycline transactivator (tTA) in forebrain neurons. Offsping were then crossed to the Tg21221 line with a responder transgene of wildtype human tau. APP: Transgenic; PSEN1: Transgenic; MAPT: Transgenic Alzheimer's Disease Tau accumulations, dystrophic neurites, astrocytosis, neuronal loss, and synapse loss were more pronounced adjacent to cortical plaques. Tangles were not observed. No data. N/A APPswe/PSEN1dE9 mice available through JAX MMRRC Stock# 034829. Jackson et al., 2016 Yes
<p>-</p>, <p>APP/PS1</p>, <p>C57BL/6J APPswePsen1de9</p>, <p>B6.APB<sup>Tg</sup></p> B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax C57BL/6J APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on the original hybrid C57BL/6 x C3H background were backcrossed with C57BL/6J mice. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques begin to emerge in the cortex at about 4 months of age and in the hippocampus at about 6 months. Gliosis and dystrophic neurites are associated with plaques. Amyloid angiopathy has been observed in the retina. Hyperactivity is apparent by 6 months. Deficits in the Morris water maze emerge between 6 and 10 months and worsen with age. A substantial proportion of APPswe/PSEN1dE9 mice exhibit electrographic and behavioral seizures. Available from the Jackson Laboratory, JAX MMRRC Stock# 034832 (formerly Jackson Lab Stock #005864) Minkeviciene et al., 2008, Minkeviciene et al., 2009 Yes
<p>-</p>, <p>APP/PS1</p>, <p>APPswe/PS1deltaE9</p>, <p>line 85</p>, <p>APP(swe) + PSEN1DeltaE9</p>, <p>APPdE9</p>, <p>Borchelt mice</p> B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax C57BL/6;C3H APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 Co-injection of a vector for chimeric mouse/human APP carrying the Swedish mutation and a second for mutant PSEN1 (deltaE9) controlled by independent mouse prion protein promoter elements. The two transgenes co-integrated and co-segragate as a single locus. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Occasional Aβ deposits by 6 months with abundant plaques in the hippocampus and cortex by 9 months and a progressive increase in plaques up to 12 months. No tangles. Decrease in synaptic markers and increase in complement immunoreactivity. Cognitive impairment (e.g., deficits in spatial memory and contextual memory). Changes in spontaneous behavior (e.g., nest-building, burrowing). Kinked tail phenotype that is believed to be due to genetic background. The Jackson Lab; available through the JAX MMRRC Stock# 034829 (formerly Jackson Lab Stock # 004462); Live Jankowsky et al., 2001, Jankowsky et al., 2004 Yes
CAST.Cg-Tg(APPswe,PSEN1dE9)85Dbo/How CAST/EiJ APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on a congenic C57BL/6J background were backcrossed with CAST/EiJ mice for at least six generations. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, plaque-associated gliosis, cerebral amyloid angiopathy; possible neuron loss in hippocampal area CA1. Transgenic mice are hyperactive. Working memory (spontaneous alternation in the Y-maze) is normal at 7 to 8 months, but short-term memory (tested in the Y-maze) is impaired in males (data from females is not available, as wild-type females are unable to perform this test). Available from The Jackson Laboratory, Stock #25973. Onos et al., 2019 Yes
<p>-</p>, <p>PS19-T2<sup>R47H</sup></p>, <p>PS19-TREM2<sup>R47H</sup></p> 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
PWK.Cg-Tg(APPswe,PSEN1dE9)85Dbo/How PWK/PhJ APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on a congenic C57BL/6J background were backcrossed with PWK/PhJ mice for at least six generations. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques and plaque-associated gliosis by 8 months. Transgenic mice are hyperactive and aggressive. Working memory and short-term memory are intact at 7 to 8 months, as assessed by tests in the Y-maze. Available from The Jackson Laboratory, Stock #25971. Onos et al., 2019 Yes
<p>-</p>, <p>Trem2<sup>-/-</sup> (Colonna)</p> C57BL/6 -TREM2tm1cln C57BL/6 Trem2 Inactivation of the mouse Trem2 gene by targeted deletion of exons 3 and 4 Trem2: Knock-Out Nasu-Hakola Disease, Frontotemporal Dementia, Alzheimer's Disease Microglial number remains constant and microglial size decreases with age in the corpus callosum of Trem2 KO mice, while microglial number increases and microglial size remains stable in wild-type mice. No cognitive/behaviorial deficits observed. Osteopenic. Impaired microglial response to experimental demyelination, middle cerebral artery occlusion, and facial nerve axotomy. Available through Marco Colonna Turnbull et al., 2006 Yes
<p>-</p>, <p>Trem2<sup>-/-</sup>5XFAD</p>, <p>mTrem2<sup>-/-</sup>5XFAD</p><p>&nbsp;</p> C57BL/6 -TREM2tm1cln; B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmja C57BL/6 Trem2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V 5XFAD mice were crossed with Trem2 KO mice. TREM2 KO: Targeted deletion of exons 3 and 4 of mouse Trem2. 5XFAD express two transgenes: 1) human APP with the Swedish, Florida and London mutations, containing the 5' untranslated region and driven by the mouse Thy1 promoter and 2) human PSEN1 with the M146L and L286V mutations driven by the mouse Thy1 promoter. Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Compared with 5XFAD, mice deficient in TREM2 show an age- dependent increase in amyloid accumulation in the hippocampus, more severe plaque-associated neuritic dystrophy, and exaggerated neuron loss in the cortex. Microglial containment of plaques is compromised in TREM2-deficient animals. Microglia accumulate autophagosomes. No data. Trem2 KO: available through Marco Colonna. 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live Wang et al., 2015 Yes
<p>-</p>, <p>APPPS1;Trem2<sup>-/-</sup></p> 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
<p>-</p>, <p>TREM2 Reporter Mouse</p> B6J-Trem2em4(mKate2)Bwef C57Bl/6J CRISPR/Cas9 gene editing was used to insert the reporter construct into the mouse Trem2 locus, immediately downstream of exon 5. This construct contained a P2A (peptide 2A) sequence followed by mKate2 with the KDEL endoplasmic reticulum-retention sequence fused to its C terminus. Silent mutations were also introduced into Trem2 to aid in genotyping. Alzheimer's Disease, Frontotemporal Dementia, Nasu-Hakola Disease Unknown. Unknown. Bicistronic expression of endogenous Trem2 and the fluorescent protein mKate2 under control of the endogenous Trem2 promoter. Available through Christian Haass. Feiten et al. No
<p>-</p>, <p>Trem2<sup>+/R47H</sup></p> 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
<p>-</p>, <p>APPPS1-21;Trem2<sup>+/R47H</sup></p> 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
WSB.Cg-Tg(APPswe,PSEN1dE9)85Dbo/How WSB/EiJ APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on a congenic C57BL/6J background were backcrossed with WSB/EiJ mice for at least six generations. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, plaque-associated gliosis, cerebral amyloid angiopathy; possible neuron loss in cortex and hippocampal area CA1 in females. Transgenic mice are hyperactive. Working memory (spontaneous alternation in the Y-maze) is normal at 7 to 8 months, but short-term memory (tested in the Y-maze) is impaired in females (data from males is not available, as wild-type males are unable to perform this test). Available from The Jackson Laboratory, Stock #25970. Onos et al., 2019 Yes
Rat Models (1)
Fischer 344 APP, PSEN1 APP K670_M671delinsNL (Swedish), APP V717F (Indiana), PSEN1 L166P APP+PS1 transgenic rats express human APP with the Swedish and Indiana mutations and human PSEN1 with the L166P mutation. Both transgenes are driven by the ubiquitin-C promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, cerebral amyloid angiopathy, and necrotic neurons in hippocampus and cortex by 19 months of age. Deficits in Barnes maze by 10 months of age. Unknown. Agca et al., 2016, Klakotskaia et al., 2018 Yes