Research Models

Selected Results

1 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 (1)
<p>PDGF-APPSw,Ind</p>, <p>PDGF-hAPP695,751,770V171F, KM670/671NL</p>, <p>hAPPJ20</p>, <p>hAPP</p>, <p>Mucke mice</p> B6.Cg-Zbtb20Tg(PDGFB-APPSwInd)20Lms/2Mmjax C57BL/6 APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana) Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter. APP: Transgenic Alzheimer's Disease Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptic markers and increase in complement immunoreactvity. Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated. On the C57BL/6J background hippocampal hyperexcitability was observed and cortical and hippocampal spontaneous nonconvulsive seizures. The Jackson Lab; available through the JAX MMRRC Stock# 034836-JAX; Live Mucke et al., 2000 Yes

1 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+.

J20 (PDGF-APPSw,Ind)

Observed
  1. X
    Plaques at 22

    At 5-7 months of age diffuse amyloid-β plaques deposit in the dentate gyrus and neocortex. Amyloid deposition is progressive with widespread plaques by 8-10 months. Aβ puncta are deposited in the hippocampus as early as 1 month (Hong et al., 2016).

  2. X
    Neuronal Loss at 12

    Cell loss varies by brain region. No significant neuronal loss was observed in the CA3 region of the hippocampus at 6, 12, 24 and 36 weeks of age nor in the CA1 region at 6 weeks; however, at 12, 24, and 36 weeks significant neuronal loss was observed in the CA1 region compared to age-matched wild-type animals (Wright et al., 2013).

  3. X
    Gliosis at 24

    At 24 and 36 weeks a significant increase in the number of reactive GFAP+ astrocytes and CD68+ microglia was observed in the hippocampi of J20 mice compared to age-matched wild-type controls. No significant difference was observed at 6 and 12 weeks (Wright et al., 2013).

  4. X
    Synaptic Loss at 15

    Age-dependent loss of synaptophysin, synaptotagmin, PSD-95, and homer immunoreactivity in the hippocampus by 3 months; synapse loss was confirmed by electron microscopy. No significant difference was seen at 1 month (Hong et al., 2016).

  5. X
    Changes in LTP/LTD at 13

    Basal synaptic transmission is impaired between 3-6 months; extracellularly recorded field EPSPs at the Schaffer collateral to CA1 synapse in acute hippocampal slices were on average smaller in amplitude than those seen in wild-type mice. Significant deficits in LTP at the Schaffer collateral–CA1 synapse compared with control mice at 3-6 months (Saganich et al., 2006).

  6. X
    Cognitive Impairment at 16

    Deficits in spatial memory and learning appear as the mice age. By 4 months, J20 mice demonstrate spatial reference memory deficits as measured by the radial arm maze (Wright et al., 2013) and Morris water maze (Cheng et al., 2007).

Absent
  • Tangles at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana) APP: Transgenic Alzheimer's Disease

Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptic markers and increase in complement immunoreactvity.

Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated.

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