Transgenic Mice Expressing Human Myeloperoxidase
Introduction Myeloperoxidase (MPO) co-localizes with macrophages in the human artery wall, and its characteristic oxidation products have been detected in atherosclerotic lesions. Thus, oxidants produced by the enzyme might promote atherosclerosis. However, macrophages in mouse atherosclerotic tissue do not express MPO. Therefore, mice are an inappropriate model for testing the role of MPO in vascular disease. To overcome this problem, UW researchers generated transgenic (Tg) mice containing the human MPO gene. Technology description Transgenic mice expressing human MPO (h-MPO) were produced using a Visna virus promoter. To confine MPO expression to macrophages, LDL receptor– deficient mice were lethally irradiated and their bone marrow was repopulated with cells from wild-type mice or MPO-Tg mice. Mice repopulated with h-MPO-Tg bone marrow developed significantly larger lesions than did mice transplanted with WT marrow. Thus, expression of h-MPO in macrophages promoted the development of atherosclerotic lesions in mice. Business opportunity Atherosclerosis, the leading cause of premature death in Western societies, is a chronic inflammatory disease. Observations indicate that expression of human MPO in macrophages promotes atherosclerosis in hypercholesterolemic mice, raising the possibility that the enzyme might be a potential therapeutic target for preventing cardiovascular disease in humans. These transgenic mice could be useful for discovering and testing new drugs. Intellectual property position The mice are available for licensing under non-exclusive bailment. Related Publication(s)
McMillen TS, Heinecke JW and LeBoeuf RC: Expression of human myeloperoxidase by macrophages promotes atherosclerosis in mice. Circulation 111:2798-2804, 2005.
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