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Scientists Establish New Canine Mutant Model to Mimic Human Cerebrovascular Disease

Sep 24, 2021

A research group led by Dr. ZHANG Yongqing from the Institute of Genetics and Developmental Biology (IGDB) of the Chinese Academy of Sciences reported that in the new canine mutant model they established, the apolipoprotein E (ApoE) knockout dogs showed severe arteriosclerosis, faithfully mimicking human cerebrovascular disease. 
As people's living standards improve and their eating habits change, stroke and coronary artery diseases caused by arteriosclerosis have become the leading causes of death worldwide. Dyslipidemia is a major contributor for arteriosclerosis, and ApoE plays a key role in cholesterol metabolism.
ApoE mutant mice and rats showing elevated cholesterol levels have been widely used for arteriosclerosis study. However, these animal models rarely exhibit severe arteriosclerosis and related clinical symptoms, limiting their use in translational research. Dogs are anatomically, physiologically, and metabolically closer to humans than mice, making them potentially ideal models for cerebrovascular disease.       
By using Magnetic Resonance Imaging, ultrasonic diagnosis, and multi-omic analysis, the researchers revealed that ApoE knockout dogs exhibited extensive and severe arteriosclerosis plaques, arterial stenosis and occlusion, thrombosis, and, ultimately, stroke and gangrene.
The most important clinical consequences of arteriosclerosis in humans were lesions in the cerebral arteries and coronary arteries, which were fully replicated in adult mutant dogs. 
These results indicate that the ApoE mutants may be better suited for basic and translational research in arteriosclerosis and related diseases compared with other genetic mutant species.
These findings were recently published online in the Journal SCIENCE CHINA Life Sciences.
 
The basilar artery and coronary artery in the brain of an ApoE homozygous mutant dog were narrowed and occluded due to severe arteriosclerosis. (Image by IGDB)
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ZHANG Yongqing

Institute of Genetics and Developmental Biology

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Dogs lacking Apolipoprotein E show advanced atherosclerosis leading to apparent clinical complications

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