Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1006-1014
Published online before print April 15, 2004, doi: 10.1161/01.ATV.0000128849.12617.f4
Published online before print April 15, 2004, doi: 10.1161/01.ATV.0000128849.12617.f4
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© 2004 American Heart Association, Inc.
Brief Reviews |
Atherosclerosis in the Apolipoprotein E–Deficient Mouse
A Decade of Progress
From the Department of Pathology (K.S.M.), the Center for Research, Prevention, and Treatment of Atherosclerosis (K.S.M., E.L.), and the Department of Internal Medicine B (E.L.), Hadassah University Hospital, Jerusalem, Israel.
Correspondence to Dr Eran Leitersdorf, Department of Medicine B, Hadassah University Hospital, Kiryat Hadassah, P.O.B. 12221, Jerusalem 91120, Israel. E-mail eranL{at}hadassah.org.il
Arguably the most critical advancement in the elucidation of factors affecting atherogenesis has been the development of mouse models of atherosclerosis. Among available models, the apolipoprotein E–deficient (apoE–/–) mouse is particularly popular because of its propensity to spontaneously develop atherosclerotic lesions on a standard chow diet. A Medline search reveals over 645 articles dedicated to studies using this reliable and convenient "super" animal model since its inception (Piedrahita JA et al, Proc Natl Acad Sci U S A 1992;89:4471–4475; Plump AS et al, Cell 1992;71:343–353) with a more or less steady increase from year to year. This review will examine our present understanding of the pathology and progression of plaques in this animal and highlight some of the nutritional, pharmacological, and genetic studies that have enhanced this understanding.
The apolipoprotein E–deficient (apoE–/–) mouse is currently the most popular murine model used for atherosclerotic studies. This review outlines the uses and limitations of, and plaque pathology in this mouse, and highlights some of the more recent work on nutritional, pharmacological, and most significantly, genetic factors affecting atherogenesis in this versatile model.
Key Words: apolipoprotein E • atherosclerosis • knockout • mouse model
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|
|
|
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|
|
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