Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, Texas
Physiol Genomics. 2017 Nov 1;49(11):601-617. doi: 10.1152/physiolgenomics.00065.2017. Epub 2017 Sep 15.
The application of gene mapping methods to uncover the genetic basis of hypertension in the inbred spontaneously hypertensive rat (SHR) began over 25 yr ago. This animal provides a useful model of genetic high blood pressure, and some of its features are described. In particular, it appears to be a polygenic model of disease, and polygenes participate in human hypertension genetic risk. The SHR hypertension alleles were fixed rapidly by selective breeding in just a few generations and so are presumably common genetic variants present in the outbred Wistar strain from which SHR was created. This review provides a background to the origins and genesis of this rat line. It considers its usefulness as a model organism for a common cardiovascular disease. The progress and obstacles facing mapping are considered in depth, as are the emergence and application of other genome-wide genetic discovery approaches that have been applied to investigate this model. Candidate genes, their identification, and the evidence to support their potential role in blood pressure elevation are considered. The review assesses the progress that has arisen from this work has been limited. Consideration is given to some of the factors that have impeded progress, and prospects for advancing understanding of the genetic basis of hypertension in this model are discussed.
应用基因图谱方法来揭示自发性高血压大鼠（SHR）中高血压的遗传基础的研究始于 25 年前。这种动物提供了一个有用的遗传性高血压模型，本文将对其特征进行描述。特别是，它似乎是一种多基因疾病模型，多基因参与了人类高血压的遗传风险。通过在短短几代内的选择性繁殖，SHR 的高血压等位基因迅速固定下来，因此可以推测它们是源自 SHR 所创建的杂交 Wistar 品系中的常见遗传变异。本文回顾了该大鼠品系的起源和发生过程。本文还考虑了它作为一种常见心血管疾病模型生物的有用性。本文深入探讨了基因图谱的进展和障碍，以及已经应用于该模型研究的其他全基因组遗传发现方法的出现和应用。本文还考虑了候选基因的鉴定及其对血压升高的潜在作用的证据。本文评估了从这项工作中取得的进展是有限的。本文考虑了一些阻碍进展的因素，并讨论了在该模型中推进对高血压遗传基础的理解的前景。
