© 1999 American Heart Association, Inc.
Review |
Vascular Biology in Genetically Altered Mice
Smaller Vessels, Bigger Insight
From the Departments of Internal Medicine, Pharmacology, and Physiology and Biophysics, Cardiovascular Center, University of Iowa College of Medicine, Iowa City.
Correspondence to Frank M. Faraci, PhD, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242-1081.
Key Words: endothelial function • pathophysiology • nitric oxide • vascular biology • gene-targeted mice
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Introduction |
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Manipulation of genes in the mouse genome to produce transgenic or gene-targeted animals represents a powerful experimental tool with which to study the role of specific gene products in complex physiological systems. Because of the power of studying genetically altered mice, a major effort has begun to incorporate the use of these models in studies of the cardiovascular system, including vascular biology.
The present review will summarize progress that has been made in studies of vascular biology in mice. A major focus of the discussion will be studies of vascular function. At present, the majority of studies of vascular function in genetically altered mice have been related to the role of endothelium. For this reason, we will highlight studies related to endothelium and nitric oxide (NO, a major vasoactive substance produced by endothelium) as examples of the types of studies that are being done in mice and of the new insight into the regulation of blood vessels that is emerging.
The article will also summarize advantages and limitations of using genetically altered mice as well as new insights obtained from such studies in the areas of signal transduction and pathophysiology. In addition, we will summarize potential directions and methodologies for future studies of vascular biology in mice.
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Use of Normal Mice for Studies of Vascular Biology |
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The methodology to produce targeted gene disruption in mammalian cells that subsequently contribute to the germ line was developed in the mid to late 1980s.1 2 3 4 5 Before the age of producing genetically altered mice, studies of vascular function in mice appeared only occasionally in
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