New Alzheimer’s Mouse Model Better Characterizes Human Disease

Apr 02 2012

Charles River Discovery Research Services (DRS) recently validated the CVN Alzheimer’s mouse line. This model can be used to investigate amyloid beta-based therapies as well as tau, inflammation, symptomatic changes and CBF-related approaches. Through a recent expansion of this colony, CVN mice are now available for studies.

CVN Alzheimer’s mice better reflect the cascade of disease in humans due to the fact that they address early amyloid deposition and inflammation through to later-staged hyperphosphorylated and aggregated native tau pathology. 

In comparison to other mouse models of Alzheimer’s, such as the B6; SJL-Tg (APPSWE) 2576kha TG2576, the CVN mouse shows more Alzheimer-related pathologies at an earlier age. In addition, factors not present in the TG2576, like neurovascular involvement, cell death and tau phosphorylation, can be found in the CVN mouse.

CVN Model History

Researchers at the Division of Neurology, Department of Medicine at Duke University Medical Center in conjunction with the Department of Medicine, Stony Brook University developed this mouse line by genetic deletion of nitric oxide synthase 2 (NOS2; iNOS) in APPSwDI mouse strains (Wilcock et al. 2008). Rationale for reducing NOS2 in this mouse was based on the immunosuppression of NOS2 in chronic inflammatory diseases. NOS2 deletion combined with multiple amyloid precursor protein (APP) mutations enhances the pathology and drives the phenotype toward human Alzheimer’s features.

Technical Information About CVN Model

The homozygous bigenic CVN mouse (APPSwDI/NOS2-/-) progresses from Aβ production and amyloid deposition to hyperphosphorylated normal mouse tau at Alzheimer's disease-associated epitopes. The aggregation and redistribution of tau to somatodendritic regions of neurons causes significant neuronal loss (including loss of interneurons), moderate-to-severe cerebral amyloid angiopathy (CAA), and severe learning and memory deficits. Inflammation, another characteristic of human Alzheimer's, is shown in this model by microglial/macrophage activation and expression of certain chemokines and cytokines. Vascular changes, including CAA and related CBF disturbances are detected by multimodal MRI techniques late in the disease progression.

For more information or to inquire about placing a study using this newly validated CVN Alzheimer’s mouse model, please contact us at askcharlesriver@crl.com.