Atherosclerosis and the mouse: a decade of experience.
Atherosclerotic disease is the leading killer in Western societies, accounting for close to 50% of deaths. Relatively little is known about the genetics of this disease in the general population despite its high prevalence. Several experimental systems exist for studying the pathology of this disease, but these larger animal models fail to offer insights into the genetics. Over the past decade the mouse has supplanted larger animal models of atherosclerosis to become the primary organism for the study of atherosclerosis genetics and, to some extent, pathophysiology. Lipoprotein biologists in particular have benefited from the ability to modify the mouse genetically to study the relationship of lipoprotein abnormalities to atherosclerosis. Given the complexity of the disease an in vivo system is requisite and since the mid-1980s the mouse has served as that system. Initial studies using classical mouse genetics first defined differing susceptibilities to atherosclerosis among distinct strains of mice. These studies acted at least in part to shed preconceptions among lipoprotein and vascular biologists that the mouse could not serve as an atherosclerosis model. Subsequent studies taking advantage of the ability to overexpress and knock genes out have advanced understanding of the in vivo function of genes involved in lipoprotein transport and the relationship between these genes (and their attendant lipoprotein disorders) and atherosclerotic disease. This review chronicles the advances made over the past 10 years and reviews the contribution that the mouse has provided lipoprotein and atherosclerosis research.
Plump
A
A
The Rockefeller University, New York, NY 10021-6399, USA. andyp@itsa.ucsf.edu
D000818:Animals; D001054:Apolipoproteins A / Q000502:physiology; D001161:Arteriosclerosis / Q000235:genetics*; D004195:Disease Models, Animal; D008074:Lipoproteins / Q000235:genetics / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000502:physiology; D008079:Lipoproteins, VLDL / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D001054:Apolipoproteins A; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL