Kren V, Pravenec M, Lu S, Krenova D, Wang J M, Wang N, Merriouns T, Wong A, St Lezin E, Lau D, Szpirer C, Szpirer J, Kurtz T W
Institute of Biology, First Medical Faculty, Charles University, Prague, Czech Republic.
J Clin Invest. 1997 Feb 15;99(4):577-81. doi: 10.1172/JCI119198.
The spontaneously hypertensive rat (SHR) is the most widely studied animal model of essential hypertension. Despite > 30 yr of research, the primary genetic lesions responsible for hypertension in the SHR remain undefined. In this report, we describe the construction and hemodynamic characterization of a congenic strain of SHR (SHR-Lx) that carries a defined segment of chromosome 8 from a normotensive strain of Brown-Norway rats (BN-Lx strain). Transfer of this segment of chromosome 8 from the BN-Lx strain onto the SHR background resulted in substantial reductions in systolic and diastolic blood pressure and cardiac mass. Linkage and comparative mapping studies indicate that the transferred chromosome segment contains a number of candidate genes for hypertension, including genes encoding a brain dopamine receptor and a renal epithelial potassium channel. These findings demonstrate that BP regulatory gene(s) exist within the differential chromosome segment trapped in the SHR-Lx congenic strain and that this region of chromosome 8 plays a major role in the hypertension of SHR vs. BN-Lx rats.
自发性高血压大鼠（SHR）是研究最为广泛的原发性高血压动物模型。尽管经过了30多年的研究，但导致SHR高血压的主要基因损伤仍未明确。在本报告中，我们描述了一种同源近交系SHR（SHR-Lx）的构建及其血液动力学特征，该品系携带了来自正常血压的挪威棕色大鼠品系（BN-Lx品系）第8号染色体的一个特定片段。将第8号染色体的这个片段从BN-Lx品系转移到SHR背景上，导致收缩压和舒张压以及心脏重量大幅降低。连锁和比较定位研究表明，转移的染色体片段包含多个高血压候选基因，包括编码脑多巴胺受体和肾上皮钾通道的基因。这些发现表明，血压调节基因存在于SHR-Lx同源近交系捕获的差异染色体片段中，并且第8号染色体的这个区域在SHR与BN-Lx大鼠的高血压形成中起主要作用。
