Ribatti Domenico
Department of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy.
Int Rev Cell Mol Biol. 2008;266:1-35. doi: 10.1016/S1937-6448(07)66001-8.
The development of transgenic technologies in mice has allowed the study of the consequences of genetic alterations on angiogenesis and lymphangiogenesis. This review summarizes the murine models currently available for studies involving the manipulation of angiogenesis and lymphangiogenesis. Abnormal embryonic vascular development, resulting from defects in the formation of a primitive vascular plexus, has been observed in mice lacking vascular endothelial growth factor, vascular endothelial growth factor receptor-1 and -2, transforming growth factor-beta, fibronectin, or vascular endothelial cadherin. Defects in the expansion and remodeling of the embryonic vasculature occur in mice deficient in Tie-1, Tie-2, or angiopoietin-1, and in mice overexpressing neuropilin or angiopoietin-2. Impaired recruitment and investment of mural cells have been observed in mice with disruption of the genes encoding platelet-derived growth factor-B, platelet-derived growth factor-B receptor, and tissue factor. Gene-targeting experiments in mice have identified the EphB/ephrinB system as a critical and rate-limiting determinant of arteriovenous differentiation during embryonic vascular development. Vascular endothelial growth factor-C is necessary for the initial sprouting and migration of lymphatic endothelial cells from embryonic veins, and mice lacking vascular endothelial growth factor-C die prenatally, whereas vascular endothelial growth factor-D is dispensable for embryonic lymphatic development.
小鼠转基因技术的发展使得研究基因改变对血管生成和淋巴管生成的影响成为可能。本综述总结了目前可用于涉及血管生成和淋巴管生成操纵研究的小鼠模型。在缺乏血管内皮生长因子、血管内皮生长因子受体-1和-2、转化生长因子-β、纤连蛋白或血管内皮钙黏蛋白的小鼠中，已观察到由于原始血管丛形成缺陷导致的异常胚胎血管发育。在缺乏Tie-1、Tie-2或血管生成素-1的小鼠以及过表达神经纤毛蛋白或血管生成素-2的小鼠中，胚胎血管系统的扩张和重塑出现缺陷。在编码血小板衍生生长因子-B、血小板衍生生长因子-B受体和组织因子的基因被破坏的小鼠中，已观察到壁细胞的募集和包绕受损。小鼠中的基因靶向实验已确定EphB/ephrinB系统是胚胎血管发育过程中动静脉分化的关键和限速决定因素。血管内皮生长因子-C对于胚胎静脉中淋巴管内皮细胞的初始芽生和迁移是必需的，缺乏血管内皮生长因子-C的小鼠在产前死亡，而血管内皮生长因子-D对于胚胎淋巴管发育是可有可无的。
