Mouse Models of Spontaneous Thrombosis
Thrombosis comes in two flavours: VT: Venous thrombosis (with pulmonary embolism as possible results) and AT: Arterial thrombosis (with myocardial infarction or stroke as possible result). Venous and arterial thrombosis are a major source of morbidity and mortality worldwide and both are complex vascular diseases for which pathogenesis is incompletely understood. Animal models are fundamental in our effort to understand the disease and develop better therapy (“Holy Grail” an antithrombotic without bleeding risk as side-effect). Currently there are limited (venous thrombosis) or no (arterial thrombosis) technically reproducible or clinically relevant mouse models for these diseases.
Researchers at the LUMC have developed a mouse model for VT via “humanizing” mouse coagulation via RNAi of the hepatic antithrombin (Serpinc1) and protein C (Proc) genes.
In addition, they have developed a mouse model for AT via RNAi of Proc in Apoe-/- mice. In initial studies organized and large thrombi superimposed on an aortic root atherosclerotic plaque were observed, a unique and novel finding. This model needs further optimization.
Figure 1: MRI of spontaneous venous thrombosis in a large vessel in the head (mandibular area)
[Figure 2: Arterial (athero)thrombosis in apoliporotein E deficient mouse following RNAi]
Potential applications would be in preclinical research of venous thrombosis and pulmonary embolism, and arterial thrombosis and myocardial infarction and stroke.
Know-how on the VTE model is available for partnering and/or licensing. LUMC are seeking co-development partners to further optimize the AT model and/or study its response to drugs that are currently used in MI/stroke (lipid-lowering/antiplatelet drugs) and to those in current pipelines (PAR inhibitors, FXI inhibitors, others).
Keywords: animal model, mouse model, thrombosis, atherothrombosis, venous thrombosis
- Generates highly reproducible acute venous thrombosis
- Is technically simple and fast
- Reproduces morphologically venous thrombosis in humans
- Is responsive to (pharmacological) thrombin and platelet inhibition
- Is used by LUMC researchers and others to study VT pathogenesis
Luris reference numberINV-0700.0875
VTE model: published. AT model: initial findings published, optimized model might be patented.