Research Models

Selected Results

3 Models

Name Other Names Strain Name Genetic Background Gene Mutation Modification Info Modification Disease Neuropathological
Phenotype
Cognition/ Behavior Other Phenotype Availability Primary Paper Visualization
Mouse Models (3)
-, APPxPS1, APP(V717I)x PS1(A246E), APP[V717I]x PS1[A246E], APP.V717I x PS1.A246E Thy1-hAPP.V717I ( C57BL/6)x Thy1-hPS1.A246E (FVB/N) Originally generated on FVB/N background; available at reMYND as C57BL/6xFVB/N APP, PSEN1 APP V717I (London), PSEN1 A246E The transgene overexpresses the mutant human amyloid protein precursor APP (isoform 695), which bears the London (V717I) mutation, and human presenilin-1 with the A246E mutation, both under the control of the neuron-specific murine Thy1 promoter. APP: Multi-transgene; PSEN1: Transgenic; Alzheimer's Disease, Cerebral Amyloid Angiopathy Soluble, oligomeric Aβ at 2 months and increases with age. Amyloid plaques at 6-9 months, earlier than APP(V717I) single transgenics. Plaques start in the subiculum and spread to the frontal cortex. Amyloid-associated inflammation. CAA pathology at 8 months; microbleeds at 12-15 months. Dystropic neurites containing hyperphosphorylated tau, but no tangle pathology. From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris Water Maze. Impaired associative learning, hyperactivity, anxiety, and aggression. Available through reMYND Dewachter et al., 2000 Yes
-, APPSwe (line C3-3)/PSEN1(A246E), APP/PS1 B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J Origin: (C57BL/6J x C3H/HeJ)F2 APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 A246E Double transgenic mice; cross of mice expressing the human PSEN1 gene with the A246E mutation under the control of the mouse prion protein promoter with mice expressing chimeric APP (isoform 695) with the Swedish mutation also under the control of the mouse prion promoter. The chimeric APP molecule was created by replacing the mouse Aβ sequence with the cognate human sequence. APP: Transgenic; PSEN1: Transgenic; Alzheimer's Disease Elevated Aβ42(43) peptide in the brain. By 9 months develop amyloid deposits in the cortex and hippocampus which become more numerous by 10-12 months. Dystrophic neurites associated with gliosis in the cortex and hippocampus. Aβ42 and Aβ40 codeposit. Poor nest building. Reduced retention on learned passive avoidance task. Increased immobility time in forced swim task.

Increased irritability.

Jackson Labs: Stock# 003378; Cryopreserved Borchelt et al., 1997, Borchelt et al., 1996 Yes
FVB/N PSEN1 PSEN1 A246E Transgene human PSEN1 with the A246E mutation driven by the mouse thy1 promoter. PSEN1: Transgenic Alzheimer's Disease Histologically normal up to 2 years old by hematoxylin-eosin, silver, and thioflavin-S staining. Learning and spatial memory were unaffected in the water maze test. Neither the escape latency nor escape pathway was different from PSEN1 wild-type mice at 1 and 9 months of age.

Mice are more sensitive to kainic acid displaying greater KA-induced seizure activity and neuronal damage. LTP induced by a strong stimulus was not altered, but a weak stimulation at synapses between Schaeffer’s collaterals and CA1 pyramidal neurons elicited LTP only in mutant mice.

Unknown Schneider et al., 2001 No

2 Visualizations

Phenotypes Examined

  • Plaques
  • Tangles
  • Neuronal Loss
  • Gliosis
  • Changes in LTP/LTD
  • Cognitive Impairment

When visualized, these phenotypes will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 1yr, 15mo, 18mo+.

APP(V717I) x PS1(A246E)

Observed
  1. Plaques at 17

    Plaques start in cortex, hippocampus and subiculum at 4-6 months.

  2. Gliosis at 20

    Elevated GFAP, microglial activation, and other markers of brain inflammation increase as of 4.5 months.

  3. Changes in LTP/LTD at 26

    Significant deficit in LTP in CA1 region of the hippocampus at 6 months.

  4. Cognitive Impairment at 22

    From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris water maze and other tests. Also deficits in associative learning.

Absent
  • Tangles at

    Dystrophic neurites containing hyperphosphorylated murine tau, but no tangle pathology.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological Behavioral
Phenotype
APP, PSEN1 APP V717I (London), PSEN1 A246E APP: Multi-transgene; PSEN1: Transgenic; Alzheimer's Disease, Cerebral Amyloid Angiopathy

Soluble, oligomeric Aβ at 2 months and increases with age. Amyloid plaques at 6-9 months, earlier than APP(V717I) single transgenics. Plaques start in the subiculum and spread to the frontal cortex. Amyloid-associated inflammation. CAA pathology at 8 months; microbleeds at 12-15 months. Dystropic neurites containing hyperphosphorylated tau, but no tangle pathology.

From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris Water Maze. Impaired associative learning, hyperactivity, anxiety, and aggression.

APPSwe/PSEN1(A246E)

Observed
  1. Plaques at 39

    Elevated Aβ42(43) peptide in the brain. By 9 months develop amyloid deposits in the cortex and hippocampus which become more numerous by 10-12 months (Borchelt et al., 1997). Aβ42 and Aβ40 codeposit (Jankowsky et al., 2004).

  2. Gliosis at 52

    Reactive gliosis in the cortex and hippocampus associated with dystrophic neurites (Borchelt et al., 1997).

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    No difference in neuronal numbers in the cingulate cortex compared with wild-type animals (Xiang et al., 2002).

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological Behavioral
Phenotype
APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 A246E APP: Transgenic; PSEN1: Transgenic; Alzheimer's Disease

Elevated Aβ42(43) peptide in the brain. By 9 months develop amyloid deposits in the cortex and hippocampus which become more numerous by 10-12 months. Dystrophic neurites associated with gliosis in the cortex and hippocampus. Aβ42 and Aβ40 codeposit.

Poor nest building. Reduced retention on learned passive avoidance task. Increased immobility time in forced swim task.