Y CHROMOSOME AND HYPERTENSION

Y 染色体与高血压

• 批准号: 2224127
• 负责人: DANIEL L ELY
• 金额: $ 22.81万
• 依托单位: UNIVERSITY OF AKRON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2224127
• 关键词: autosomal recessive trait; familial hypertension; genetic strain; hormone receptor; salts; sex linked trait; spontaneous hypertensive rat; stress; sympathetic nervous system

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.

我们最近的研究表明， 自发性高血压大鼠（SHR）的高血压发生在Y 染色体 我们已经开发了两种新的，独特的F12 SHR亚株 命名为SHR/y和SHR/a，其允许操纵效应 Y染色体 SHR/y亚株含有高血压Y 染色体在正常血压的常染色体背景。 SHR/a亚株 在高血压常染色体中含有血压正常的Y染色体， 背景 这项研究的假设是， 系统和睾丸相互作用，产生升高的血压， 是性连锁的，其中一个成分是Y染色体。 完成 我们将：1）确定Y染色体对交感神经系统的影响。 神经系统反应性和睾丸，以及2）确定 高血压和正常血压患者Y染色体的遗传相互作用 基因背景 初步数据显示， 神经系统（SNS）是由高血压Y染色体调节。 通过 比较中枢和外周SNS指标、类固醇特征、盐 敏感性和盐食欲在SHR/y和SHR/a亚株，我们将 确定这些参数中哪些受Y染色体的影响。 根据我们的回交后代的结果，显性/隐性 SHR和WKY高血压常染色体基因的关系被修改 Y染色体。 SHR/y和SHR/a亚株之间的交叉， SHR和WKY将被用来研究这种相互作用。 最后， 我们的SHR/y亚系与其他血压正常的近交系大鼠的交配 将被用来确定高血压Y染色体的影响， 其他遗传背景来发现修饰基因座。