Y CHROMOSOME AND HYPERTENSION

Y 染色体与高血压

• 批准号: 2224126
• 负责人: DANIEL L ELY
• 金额: $ 21.71万
• 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/2224126
• 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）的高血压在Y上 染色体。 我们已经开发了两个新的，独特的F12 SHR基质 指定的shr/y和shr/a，可以操纵效果 Y染色体。 SHR/Y基质包含高血压Y 在正常的常染色体背景中的染色体。 SHR/A基质 在高血压常染色体中包含一个正常的Y染色体 背景。 这项研究的假设是交感神经 系统和睾丸相互作用以产生升高的血压 是性别联系的，一个组成部分是染色体。 完成 我们将：1）确定Y染色体对交感神经的影响 神经系统的反应和睾丸，2）确定 Y染色体的遗传相互作用在高血压和正常的遗传相互作用 遗传背景。 初步数据表明同情 神经系统（SNS）受到高血压Y染色体的调节。 经过 比较中央和外围SNS指标，类固醇轮廓，盐 shr/y和shr/a基德中的灵敏度和盐的食欲 确定哪些参数受Y染色体的影响。 根据我们的后代后代的结果，主要/隐性 SHR和WKY高血压常染色体基因的关系被修饰 由Y染色体。 在shr/y和shr/a基质之间交叉， SHR和WKY将用于研究这种相互作用。 最后， 我们的shr/y底座与其他正常的近交大鼠菌株的底座 将用于确定高血压Y染色体在 其他遗传背景发现修饰基因座。