Y CHROMOSOME AND HYPERTENSION

我们最近的研究表明，一个主要的遗传成分 自发性高血压大鼠(SHR)的高血压处于Y期 染色体。我们已经开发出两个新的、独特的SHR F12亚株 指定为SHR/y和SHR/a，允许操纵效果 Y染色体的基因。SHR/y亚株含有高血压Y 正常血压常染色体背景中的染色体。SHR/a亚株 高血压常染色体中含有血压正常的Y染色体 背景资料。这项研究的假设是，交感神经 系统和睾丸相互作用，产生血压升高， 是性连锁的，其中一个成分在Y染色体上。要完成 为此，我们将：1)确定Y染色体对交感神经的影响 神经系统反应性和睾丸，以及2)决定 高血压和正常血压人群中Y染色体的遗传交互作用 遗传背景。初步数据表明，同情的人 神经系统(SNS)受高血压Y染色体的调节。通过 比较中枢和外周SNS指标、类固醇谱、盐分 SHR/y和SHR/a亚株的敏感性和食盐性 确定这些参数中哪些受Y染色体的影响。 根据我们对回交后代的研究结果，显性/隐性 SHR和WKY高血压常染色体基因的关系被修改 由Y染色体决定。SHR/y和SHR/a亚系之间的杂交 SHR和WKY将被用来研究这种相互作用。最后， 我们的SHR/y亚系与其他正常血压近交系大鼠的配对 将被用来确定高血压Y染色体在 发现修饰基因座的其他遗传背景。

Our recent studies have shown that a primary genetic component of hypertension in the spontaneously hypertensive rat (SHR) is on the Y chromosome. We have developed two new, unique F12 substrains of SHR designated SHR/y and SHR/a, which allow the manipulation of the effects of the Y chromosome. The SHR/y substrain contains a hypertensive Y chromosome in a normotensive autosomal background. The SHR/a substrain contains a normotensive Y chromosome in a hypertensive autosomal background. The hypothesis of this study is that the sympathetic nervous system and the testes interact to produce an elevated blood pressure that is sex linked and one component is ont he Y chromosome. To accomplish this we will: 1) determine the impact of the Y chromosome on sympathetic nervous system responsiveness and the testes, and 2) determine the genetic interaction of the Y chromosome in hypertensive and normotensive genetic backgrounds. Preliminary data suggests that the sympathetic nervous system (SNS) is modulated by the hypertensive Y chromosome. By comparing central and peripheral SNS indicators, steroid profiles, salt sensitivity and salt appetite in the SHR/y and SHR/a substrains we will determine which of these parameters are influenced by the Y chromosome. Based on our results of backcross progeny, the dominant/recessive relationship of the SHR and WKY hypertensive autosomal genes is modified by the Y chromosome. Crosses between the SHR/y and SHR/a substrains and SHR and WKY will be used to investigate this interaction. Finally, matings of our SHR/y substrain to other normotensive inbred rat strains will be used to determine the effect of the hypertensive Y chromosome in other genetic backgrounds to discover modifier loci.