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10 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 (10)
<p>-</p>, <p>BACE1<sup>fl/fl/UbcCreER</sup> X 5xFAD</p> C57BL/6J Bace1, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V 5xFAD mice were crossed with Bace1fl/fl mice (Hu et al., 2018) to generate 5xFAD mice homozygous for a floxed Bace1 gene (“Bace1fl/fl/5xFAD). Bace1fl/fl/5xFAD mice were then bred to BACE1 conditional knock-out (Hu, Yan) mice. Bace1: Conditional Knock-out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, reactive astrocytes and microglia, and dystrophic neurites accumulate up to day 120, but to a lesser degree than in control 5xFAD (5xFAD mice homozygous for a floxed Bace1 gene), then recede thereafter. Normal contextual and cued fear conditioning, tested at 8 to 10 months of age. Deficit in long-term potentiation at Schaffer collateral–CA1 synapses in slices from 10- to 12-month-old mice, but less severe than that seen in slices from control mice (5xFAD mice homozygous for a floxed Bace1 gene). Bace1fl/fl not yet available. UBC-Cre-ERT2 available from The Jackson Laboratory, Stock# 007001. 5xFAD available from The Jackson Laboratory, JAX MMRRC Stock# 034848. Hu et al., 2018 Yes
<p>-</p>, <p>Bace1 cKO</p>, <p>BACE1<sup>fl/fl</sup>;R26CreER<sup>T2</sup>-TAM</p> C57BL6 Bace1 Mice in which exon 2 of Bace 1 is flanked by LoxP sites (Ou-Yang et al., 2018) were crossed with R26CreERT2mice (Ventura et al., 2007), which carry a transgene encoding Cre recombinase fused to the estrogen receptor, inserted at the ROSA26 locus. Bace1: Conditional Knock-out Alzheimer's Disease Defects in axonal organization. Normal learning and memory in the Morris water maze, normal alternation in the Y-maze test of working memory, and normal cued and contextual fear conditioning; possible hyperactivity in novel situations. BACE1fl/fl available through Robert Vassar; R26CreERT2 available through The Jackson Laboratory Stock# 008463, Live Ou-Yang et al., 2018 Yes
<p>-</p>, <p>BACE1 cKO</p>, <p>BACE1<sup>fl/fl/UbcCreER</sup></p> C57BL/6J Bace1 These mice were generated by crossing Bace1fl/fl mice (Hu et al., 2018), in which exon 2 of the mouse Bace1 gene is flanked by loxP sites, with UBC-Cre-ERT2 mice (The Jackson Laboratory, Stock# 007001), which carry a transgene encoding Cre recombinase fused to a modified human estrogen receptor, driven by the ubiquitin C promoter. Bace1: Conditional Knock-out Alzheimer's Disease No gross morphological changes observed. BACE1-deficient mice and Bace1fl/fl mice performed similarly in tests of contextual and cued fear conditioning at 8 to 10 months of age. Impaired long-term potentiation at Schaffer collateral–CA1 synapses in slices obtained from 10- to 12-month-old mice. Bace1fl/fl not yet available. UBC-Cre-ERT2 available from The Jackson Laboratory, Stock# 007001. Hu et al., 2018 Yes
<p>-</p>, <p>Bace1 cKO</p>, <p>BACE1<sup>fl/fl</sup>;CamKIIα-iCre</p> C57BL6 Bace1 Mice in which exon 2 of Bace1 is flanked by LoxP sites (BACE1fl/fl) were crossed with mice carrying a transgene encoding Cre recombinase driven by the CamKIIα promoter (Casanova et al., 2001). Bace1: Conditional Knock-out Alzheimer's Disease Hypomyelination and defects in axon organization. Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning. Hyperactivity in when placed in novel environments. Spontaneous behavioral seizures and epileptiform discharges in EEGs. BACE1fl/fl available through Robert Vassar;  CamKIIα-iCre available through the European Mouse Mutant Archive (EMMA) ID# EM: 01153, cryopreserved, sperm Ou-Yang et al., 2018 Yes
<p>-</p>, <p>Bace1 cKO</p>, <p>BACE1<sup>flox/flox</sup>;RosaCreERT2<sup>+/WT</sup></p> C57BL/6-Bace1tm1.1mrl C57BL/6N Bace1 Mice in which exon 2 of Bace1 is flanked by LoxP sites were crossed with R26-CreERT2 mice, which carry a transgene encoding Cre recombinase fused to the estrogen receptor, inserted at the ROSA26 locus. Bace1: Conditional Knock-out Alzheimer's Disease None observed: hippocampal mossy fiber organization and sciatic-nerve myelination were normal. Performed similarly to controls in a battery of tests (Y-maze, contextual fear conditioning, pre-pulse inhibition, open field, and light-dark transition task). Deficit in long-term potentiation at Schaffer collateral–CA1 synapses. BACE1flox/flox available through Taconic Model# 8263, Cryopreserved. RosaCreERT2 (R26-CreERT2) available through The Jackson Laboratory Stock# 008463, Live.  Lombardo et al., 2019 Yes
<p>-</p>, <p>BACE1<sup>-/-</sup></p>, <p>BACE1 KO</p> B6.129-Bace1tm1Pcw/J C57BL/6J BACE1 Homologous recombination was used to disrupt a 2kb section of BACE1 containing exon 1 replacing it with a neomycin selection cassette and the HSV thymidine kinse gene. BACE1: Knock-Out Alzheimer's Disease Hypomyelination in the hippocampus and cerebral cortex, but normal axonal development. Increased thermal pain sensitivity as measured by a hot plate test. Decreased grip strength. Homozygous mice are viable, fertile, normal in size. No BACE1 protein is detected by Western blot. Primary cultures of cortical neurons do not secrete Aβ1-40/42, Aβ11-40/42 or β-C terminal fragments (β-CTFs). The Jackson Lab: Stock# 004714; Live Cai et al., 2001 No
C57B6/C3H BACE1 Transgene of human BACE1 driven by the prion protein (PrP) promoter. BACE1: Transgenic Alzheimer's Disease No evidence of Aβ deposition in single transgenic animals. Unknown. Unknown Lee et al., 2005 No
C57BL/6 J BACE1 Wild-type human BACE driven by the murine Thy1 promoter. BACE1: Transgenic Alzheimer's Disease Not observed. Unknown. Decreased levels of full-length mature APP and increased levels of C99 and C89. Human BACE mRNA 4x higher than endogenous murine BACE. Highest expression of human BACE protein in cortex and hippocampus, lowest in cerebellum. Available through Material Transfer Management at Novartis Bodendorf et al., 2002 No
C57BL BACE1 Transgene expressing wild-type human BACE1 driven by the mouse Thy1 promoter. BACE1: Transgenic Alzheimer's Disease Not observed. Unknown. Transgene expressed in neurons only. No change in processing of endogenous murine APP. No longer available through Michael Willem Willem et al., 2004 No
hBACE1 C57BL/6J, for at least six generations BACE1 Targeted insertion of a single copy of human BACE1 at the HPRT locus on the X chromosome. Transgene expression driven by the mouse CaMKII-α promoter. BACE1: Transgenic Alzheimer's Disease Elevated extracellular multimeric Aβ, including Aβ*56 and Aβ hexamers, in the absence of plaques. At 12 months of age, astrogliosis was observed in a region- and genotype-dependent manner, especially in the dentate gyrus, hippocampal CA1, and piriform cortex. No overt tau pathology. Largely intact motor coordination and gait (Rotarod, CatWalk). Age-associated changes in multiple measures of learning and memory. Early deficits in habituation to a novel environment and semantic-like memory (three-four months). Impaired spatial learning and long-term reference (Morris water maze) and working memory (Y-maze) at six months, distinct from reduced locomotor activity and anxiety. Breeding, litter size, and overall health are normal. Reduced body weight in knock-in animals after six months of age in males and nine months in females. Available through Bettina Platt Plucińska et al., 2014 Yes

6 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+.

BACE1 cKO (Hu, Yan) X 5xFAD

Observed
  1. X
    Plaques at 11

    Accumulate up to day 120, but to a lesser degree than in control 5xFAD, then recede thereafter.

  2. X
    Gliosis at 11

    Reactive astrocytes and microglia accumulate up to day 120, but to a lesser degree than in control 5xFAD, then recede thereafter.

  3. X
    Changes in LTP/LTD at 40

    Deficit in LTP at Schaffer collateral–CA1 synapses, but less severe than in control 5xFAD mice.

Absent
  • Cognitive Impairment at

    Cued and contextual fear conditioning normal, tested at eight to 10 months of age.

No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Bace1: Conditional Knock-out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques, reactive astrocytes and microglia, and dystrophic neurites accumulate up to day 120, but to a lesser degree than in control 5xFAD (5xFAD mice homozygous for a floxed Bace1 gene), then recede thereafter.

Normal contextual and cued fear conditioning, tested at 8 to 10 months of age.

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Bace1 conditional knock-out (adult, whole body) (Vassar)

Observed
Absent
  • Changes in LTP/LTD at

    LTP at Schaffer collateral–CA1 synapses was similar in slices obtained from 12-month BACE1-deficient and control mice.

  • Cognitive Impairment at

    Normal learning and memory in the Morris water maze, normal alternation in the Y-maze test of working memory, and normal cued and contextual fear conditioning when tested at 9 months of age.

No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1 Bace1: Conditional Knock-out Alzheimer's Disease

Defects in axonal organization.

Normal learning and memory in the Morris water maze, normal alternation in the Y-maze test of working memory, and normal cued and contextual fear conditioning; possible hyperactivity in novel situations.

expand

BACE1 conditional knock-out (Hu, Yan)

Observed
  1. X
    Changes in LTP/LTD at 40

    Long-term potentiation at Schaffer collateral–CA1 synapses impaired in slices obtained from 10- to 12-month-old mice.

Absent
  • Plaques at

    Not observed.

  • Tangles at

    Not observed.

  • Neuronal Loss at

    Not observed.

  • Gliosis at

    No astrogliosis at 1-2 months.

  • Cognitive Impairment at

    Contextual and cued fear conditioning normal at 8-10 months.

No Data
  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1 Bace1: Conditional Knock-out Alzheimer's Disease

No gross morphological changes observed.

BACE1-deficient mice and Bace1fl/fl mice performed similarly in tests of contextual and cued fear conditioning at 8 to 10 months of age.

expand

Bace1 conditional knock-out (neonatal, forebrain) (Vassar)

Observed
  1. X
    Cognitive Impairment at 24

    Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning.

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.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1 Bace1: Conditional Knock-out Alzheimer's Disease

Hypomyelination and defects in axon organization.

Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning. Hyperactivity in when placed in novel environments.

expand

Bace1 conditional knockout (Tesco)

Observed
  1. X
    Changes in LTP/LTD at 60

    Deficit in long-term potentiation at Schaffer collateral–CA1 synapses in slices from 14-month-old animals that had received tamoxifen between 8 and 12 weeks of age.

Absent
  • Cognitive Impairment at

    Animals that had received tamoxifen between 8 and 12 weeks of age were tested at 4–5 or 12–14 months. Tamoxifen-treated mice performed similarly to vehicle-treated controls in the Y-maze, contextual fear conditioning, pre-pulse inhibition, open field, and light-dark transition tests.

No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1 Bace1: Conditional Knock-out Alzheimer's Disease

None observed: hippocampal mossy fiber organization and sciatic-nerve myelination were normal.

Performed similarly to controls in a battery of tests (Y-maze, contextual fear conditioning, pre-pulse inhibition, open field, and light-dark transition task).

expand

PLB4 (hBACE1)

Observed
  1. X
    Gliosis at 52

    Increased GFAP-positive astrocytes at 12 months of age in the dentate gyrus, CA1 region of the hippocampus, and the piriform cortex. Gliosis is suspected to begin earlier than 12 months.

  2. X
    Cognitive Impairment at 13

    Impaired spatial representation in a habituation task by 3 months of age. By 6 months, impaired learning and memory by a variety of tasks including the Y-maze, Morris water maze, and a test of the social transmission of food preference. These effects appear to be distinct from reduced motor activity and reduced anxiety.

Absent
  • Plaques at

    Plaques virtually absent, minimal small sparse plaques. However, prominent extracellular Aβ staining surrounding neuronal cell bodies, including Aβ multimers (e.g. Aβ*56 and Aβ hexamers).

  • Tangles at

    Preliminary analysis did not find abnormal phosphorylation or conformational changes in tau.

No Data
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
BACE1 BACE1: Transgenic Alzheimer's Disease

Elevated extracellular multimeric Aβ, including Aβ*56 and Aβ hexamers, in the absence of plaques. At 12 months of age, astrogliosis was observed in a region- and genotype-dependent manner, especially in the dentate gyrus, hippocampal CA1, and piriform cortex. No overt tau pathology.

Largely intact motor coordination and gait (Rotarod, CatWalk). Age-associated changes in multiple measures of learning and memory. Early deficits in habituation to a novel environment and semantic-like memory (three-four months). Impaired spatial learning and long-term reference (Morris water maze) and working memory (Y-maze) at six months, distinct from reduced locomotor activity and anxiety.

expand