Carmeliet P, Collen D
Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Leuven, B-3000, Belgium.
J Pathol. 2000 Feb;190(3):387-405. doi: 10.1002/(SICI)1096-9896(200002)190:3<387::AID-PATH595>3.0.CO;2-R.
Novel gene technologies have allowed us to manipulate the genetic balance of candidate molecules in mice in a controllable manner. Homologous or site-specific recombination in embryonic stem cells allows us to study the consequences of deficiencies, mutations, and conditional or tissue-specific expression of gene products in transgenic mice. These technological breakthroughs have significantly advanced biomedical research and broadened our understanding of the pathophysiological role of candidate disease genes. In addition, gene transfer allows us to test the possible therapeutic use of gene products for gene therapy. A variety of assays have been miniaturized, allowing analysis of cardiovascular physiology in the mouse. With the advent of genome sequencing programmes, these gene technologies provide means of studying 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.
新型基因技术使我们能够以可控方式操纵小鼠体内候选分子的基因平衡。胚胎干细胞中的同源重组或位点特异性重组使我们能够在转基因小鼠中研究基因产物缺陷、突变以及条件性或组织特异性表达的后果。这些技术突破极大地推动了生物医学研究，并拓宽了我们对候选疾病基因病理生理作用的理解。此外，基因转移使我们能够测试基因产物在基因治疗中的潜在治疗用途。各种检测方法已实现小型化，从而能够对小鼠的心血管生理学进行分析。随着基因组测序计划的出现，这些基因技术提供了以确凿方式研究基因功能的手段。此外，还可以建立疾病模型，用作（基因）治疗的测试模型或利用差异基因谱分析技术发现新基因的模型。本综述将聚焦于血管形成（血管生成和动脉生成）以及血管病变的分子基础。作者实验室研究过的一些选定分子将进行更详细的综述。
