CVN Mouse Model Validation Data

CVN mice are bigenic mutants that combine expression of the human APP isoform 770 containing the Swedish (K670N/M671L), Dutch (E693Q), and Iowa (D694N) mutations under the control of the mouse Thy1 promoter and a targeted loss-of-function mutation in the NOS2  gene encoding nitric oxide synthase. This Alzheimer's animal model exhibits behavioral deficits as well as biochemical hallmarks of Alzheimer's disease(AD) during aging.

There is a marked inflammatory component in this mouse compared to the Tg2576 line, and amyloid plaques and insoluble amyloid beta are detectable in mice at 9 months of age. The CVN Alzheimer's mouse model also develops hyperphosphorylated Tau aggregates and show significant neuronal loss resulting in inferior performances in learning and memory tests such as water maze and the contextual fear conditioning test.

Testing/Validation Data

Click below to see a sample data set.

The CVN Alzheimer's mouse model has been validated by multiple groups and some of the findings have been previously published. Our scientific team at the neuroscience center of excellence in Kuopio, Finland is continuously validating the CVN mouse model  using various biochemical, physiological and behavioral parameters that prove effective for Alzheimer’s Disease research.

Some of the study components used in validating CVN mice include:

Behavioral Testing

  • Barnes Maze
  • Radial Arm Water Maze
  • Morris Water Maze
  • Contextual Fear Conditioning Test
  • Touchscreen testing for cognitive deficits
  • Open Field Test for motor changes

Biochemical Analysis

  • Soluble Ab1-40 and Ab1-42 levels in cortex, plasma and CSF
  • Cytokine expression by ELISA
  • Tissue and Microdialysate samples for PK and/or Neurochemicals
Technical Sheet

Portfolio Of Validated Neurological and Rare Disease Animal Models from Charles River Drug Discovery.
Portfolio of validated neurological and rare disease animal models.

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Brain Pathology

  • Astro- and Microgliosis by GFAP and Iba-1 immunohistochemical staining
  • Phosphorylated Tau measurement
  • Cell proliferation by BrdU
  • Stereological analysis
  • Plaque load in cortex and hippocampus at 9-12 months of age

MRI

  • T2-MRI for Cerebral Volumetry
  • Proton Magnetic Resonance Spectroscopy (1H-MRS) for Hippocampal Metabolic Profile
  • Arterial Spin Labeling MRI for cerebral blood flow at older ages
  • Diffusion Tensor Imaging (DTI)
  • Pharmacological MRI (phMRI)

 

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