Vascular biology in genetically altered mice : smaller vessels, bigger insight.
Vascular biology in genetically altered mice : smaller vessels, bigger insight.
复制标题
DOI：
10.1161/01.res.85.12.1214
复制
发表时间：
1999-12
影响因子：
20.1
通讯作者：
F. Faraci;C. Sigmund
中科院分区：
文献类型：
--
作者：
F. Faraci;C. Sigmund
操纵小鼠基因组中的基因以产生转基因或以基因为靶标的动物是研究特定基因产物在复杂生理系统中作用的强大实验工具。由于研究转基因小鼠的力量，一项重大努力已经开始将这些模型的使用纳入心血管系统的研究，包括血管生物学。本文综述了近年来在小鼠血管生物学方面的研究进展。讨论的一个主要焦点将是血管功能的研究。目前，大多数关于转基因小鼠血管功能的研究都与内皮细胞的作用有关。为此，我们将重点介绍与内皮和一氧化氮(NO，内皮细胞产生的一种主要血管活性物质)相关的研究，作为正在进行的小鼠研究类型的例子，以及正在出现的对血管调节的新见解。文章还将总结使用转基因小鼠的优点和局限性，以及在信号转导和病理生理学领域从这类研究中获得的新见解。此外，我们还将总结未来小鼠血管生物学研究的潜在方向和方法。在哺乳动物细胞中产生靶向基因破坏并随后形成生殖系的方法是在20世纪80年代中后期发展起来的。1 2 3 4 5在产生转基因小鼠的年龄之前，关于小鼠血管功能的研究只是偶尔出现在文献中。6 7即使在最近几年，小鼠也只是偶尔被用于研究正常的血管功能8 9 10 11 12和检验…的效果
Manipulation of genes in the mouse genome to produce transgenic or gene-targeted animals represents a powerful experimental tool with which to study the role of specific gene products in complex physiological systems. Because of the power of studying genetically altered mice, a major effort has begun to incorporate the use of these models in studies of the cardiovascular system, including vascular biology. The present review will summarize progress that has been made in studies of vascular biology in mice. A major focus of the discussion will be studies of vascular function. At present, the majority of studies of vascular function in genetically altered mice have been related to the role of endothelium. For this reason, we will highlight studies related to endothelium and nitric oxide (NO, a major vasoactive substance produced by endothelium) as examples of the types of studies that are being done in mice and of the new insight into the regulation of blood vessels that is emerging. The article will also summarize advantages and limitations of using genetically altered mice as well as new insights obtained from such studies in the areas of signal transduction and pathophysiology. In addition, we will summarize potential directions and methodologies for future studies of vascular biology in mice. The methodology to produce targeted gene disruption in mammalian cells that subsequently contribute to the germ line was developed in the mid to late 1980s.1 2 3 4 5 Before the age of producing genetically altered mice, studies of vascular function in mice appeared only occasionally in the literature. Examples are studies of vascular responses in mice made hypertensive by psychosocial stress.6 7 Even in more recent years, mice have only occasionally been used for studies of normal vascular function8 9 10 11 12 and for examining the effects of …