Gene targeting approaches to analyzing hypertension

Essential hypertension probably results from combinations of small genetic variations that are partly normal variations and may not be appreciably har mful individually. Strategies to identify genes contributing to hypertensio n are discussed in this review. Gene targeting approaches, especially gene titration, have been used in these studies of hypertension. Gene titration experiments vary the expression of a chosen gene product by generating anim als having different numbers of copies of the gene coding for the product. Gene titration is powerful for analyzing quantitative variations seen in co mmon polygenic disorders, such as kidney diseases, diabetes mellitus, and a therosclerosis, as well as hypertension, because it allows tests of causati on by determining the effects on a phenotype by changes in expression of th e altered gene and because it matches normal quantitative variations more c losely than is possible with classic transgenic mice. The use of zero-copy (gene "knockout") animals generated by gene disruption for studies of quali tative gene effects is also discussed. These various gene targeting experim ents help identify genes regulating BP, promote a better understanding of t he pathophysiology of the condition, and help identify potential targets fo r therapies.