Y CHROMOSOME AND HYPERTENSION

Y 染色体与高血压

• 批准号: 3367198
• 负责人: DANIEL L ELY
• 金额: $ 22.88万
• 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/3367198
• 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，一个主要的遗传成分 自发性高血压大鼠 (SHR) 的高血压是在 Y 染色体。 我们开发了两种新的、独特的 SHR F12 亚系 指定为 SHR/y 和 SHR/a，允许操纵效果 Y染色体。 SHR/y 亚株包含高血压 Y 正常血压常染色体背景中的染色体。 SHR/a 亚系 高血压常染色体中含有一条血压正常的 Y 染色体 背景。 本研究的假设是交感神经 系统和睾丸相互作用导致血压升高 与性别相关，其中一个组成部分位于 Y 染色体上。 为了完成 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，2) 确定 高血压和正常血压患者 Y 染色体的遗传相互作用 遗传背景。 初步数据表明，同情心 神经系统（SNS）由高血压 Y 染色体调节。 经过 比较中枢和外周 SNS 指标、类固醇分布、盐 SHR/y 和 SHR/a 亚株的敏感性和盐食欲，我们将 确定这些参数中哪些受 Y 染色体影响。 根据我们回交后代的结果，显性/隐性 SHR和WKY高血压常染色体基因的关系被改变 由Y染色体。 SHR/y 和 SHR/a 亚系之间的杂交 SHR 和 WKY 将用于研究这种相互作用。 最后， 我们的 SHR/y 亚系与其​​他血压正常的近交系大鼠交配 将用于确定高血压 Y 染色体对 其他遗传背景来发现修饰基因座。