A research group led by Dr. ZHANG Yongqing from the Institute of Genetics and Developmental Biology (IGDB) of the Chinese Academy of Sciences reported the 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 apolipoprotein E (ApoE) plays a key role in cholesterol metabolism. The 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, 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 are lesions in the cerebral arteries and coronary arteries, which are 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.
This work was jointly done by Research Group led by Dr. ZHANG Yongqing at IGDB, Beijing SINOGENE Biotechnology Company, Professor JI Xunming from Beijing Xuanwu Hospital, and Professor LIU Enqi from Xi'an Jiaotong University Medical College.
These findings were recently published online in the Journal SCIENCE CHINA Life Sciences (Doi: 10.1007 s11427-021-2006-y).
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)
Contact:
Dr. ZHANG Yongqing
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences
