Mullins Linda J, Bailey Matthew A, Mullins John J
Molecular Physiology Laboratory, Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Physiol Rev. 2006 Apr;86(2):709-46. doi: 10.1152/physrev.00016.2005.
In this review, we outline the application and contribution of transgenic technology to establishing the genetic basis of blood pressure regulation and its dysfunction. Apart from a small number of examples where high blood pressure is the result of single gene mutation, essential hypertension is the sum of interactions between multiple environmental and genetic factors. Candidate genes can be identified by a variety of means including linkage analysis, quantitative trait locus analysis, association studies, and genome-wide scans. To test the validity of candidate genes, it is valuable to model hypertension in laboratory animals. Animal models generated through selective breeding strategies are often complex, and the underlying mechanism of hypertension is not clear. A complementary strategy has been the use of transgenic technology. Here one gene can be selectively, tissue specifically, or developmentally overexpressed, knocked down, or knocked out. Although resulting phenotypes may still be complicated, the underlying genetic perturbation is a starting point for identifying interactions that lead to hypertension. We recognize that the development and maintenance of hypertension may involve many systems including the vascular, cardiac, and central nervous systems. However, given the central role of the kidney in normal and abnormal blood pressure regulation, we intend to limit our review to models with a broadly renal perspective.
在本综述中，我们概述了转基因技术在确立血压调节及其功能障碍的遗传基础方面的应用和贡献。除了少数高血压是单基因突变结果的例子外，原发性高血压是多种环境和遗传因素相互作用的总和。候选基因可通过多种方法鉴定，包括连锁分析、数量性状基因座分析、关联研究和全基因组扫描。为了检验候选基因的有效性，在实验动物中建立高血压模型很有价值。通过选择性育种策略产生的动物模型通常很复杂，高血压的潜在机制尚不清楚。一种补充策略是使用转基因技术。在此技术中，可以选择性地、组织特异性地或在发育过程中使一个基因过度表达、敲低或敲除。尽管产生的表型可能仍然很复杂，但潜在的基因扰动是识别导致高血压的相互作用的起点。我们认识到高血压的发生和维持可能涉及许多系统，包括血管、心脏和中枢神经系统。然而，鉴于肾脏在正常和异常血压调节中的核心作用，我们打算将综述局限于从广义肾脏角度的模型。
