Transgenic mouse models in angiogenesis and cardiovascular disease

Novel gene technologies have allowed us to manipulate the genetic balance o f candidate molecules in mice in a controllable manner. Homologous or site- specific recombination in embryonic stem cells allows us to study the conse quences of deficiencies, mutations, and conditional or tissue-specific expr ession of gene products in transgenic mice. These technological breakthroug hs have significantly advanced biomedical research and broadened our unders tanding of the pathophysiological role of candidate disease genes. Tn addit ion, gene transfer allows us to test the possible therapeutic use of gene p roducts for gene therapy. A variety of assays have been miniaturized, allow ing analysis of cardiovascular physiology in the mouse. With the advent of genome sequencing programmes, these gene technologies provide means of stud ying gene function in a conclusive manner. Furthermore, disease models can be generated which can be used as test models for (gene) therapy or for the discovery of novel genes using differential gene profiling techniques. The present review will focus on the molecular basis of how blood vessels form (angiogenesis and arteriogenesis) and how they become diseased. A selected number of molecules that have been studied in the authors) laboratory will be reviewed in more detail. Copyright (C) 2000 John Wiley & Sons, Ltd.