CVN Mouse Model Validation Data
The 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. The mouse 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. In addition to exhibiting amyloid pathology, CVN mice also develop 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.
Click below to see a sample data set.
The CVN 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 research.
Some of the study components used in validating CVN mice include:
- Barnes Maze
- Radial Arm Water Maze
- Morris Water Maze
- Contextual Fear Conditioning Test
- Touchscreen testing for cognitive deficits
- Open Field Test for motor changes
- 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
- 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
- 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)