Transgenesis and gene targeting in the mouse; tools for studying genetic determinants of hypertension.
As more effort is made to identify genes responsible for hypertension in human populations and genetically hypertensive animal models, the need for experimental systems in which the functional significance of genes, gene variants, and quantitative trait loci (QTL) can be determined is becoming increasingly important. Over the past five years, transgenic and gene-targeting technology has been utilized to study the cardiovascular effects of over-expression or ablation of genes which have been considered candidates in the genetic basis of hypertension. This review focuses on the most recent major advances in this area, and how this technology aids in our understanding of the molecular mechanisms by which newly discovered genes or gene variants affect blood pressure in the whole organism. We also discuss the potential use of transgenic models in refining the location of a QTL, and discuss some of the limitations and potential pitfalls in the application of these tools to the field of hypertension research. The coupling of genetic manipulations afforded by transgenesis and gene targeting, along with advances in our ability to assess the cardiovascular phenotype in the mouse, provides us with a powerful system for examining the genes responsible for causing essential hypertension.
Department of Internal Medicine, The University of Iowa College of Medicine, Iowa City, IA 52242, USA.
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Davisson
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Sigmund