SCOR-MOLECULAR GENETICS OF HYPERTENSION

高血压的 SCOR 分子遗传学

• 批准号: 6843769
• 负责人: Curt Daniel Sigmund
• 金额: $ 230.46万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6843769
• 关键词: familial hypertension; hypertension; molecular genetics; familial hypertension; hypertension; molecular genetics

The application proposes to renew a Specialized Center of Research (SCOR) in the Molecular Genetics of Hypertension in the University of Iowa Cardiovascular Center. The overall theme is "Molecular and Physiologic Mechanisms of Genetic Hypertension in Humans and Experimental Animals." This initiative, which we have been planning for the past 18 months to fund 6 projects and one scientific core. The center brings together a cadre of investigators including outstanding molecular geneticists (Val Sheffield, Bento Soares and Curt Sigmund at Iowa and John Rapp in Ohio); molecular biologists (Peter Snyder and John Engelhardt); a genetic epidemiologist and biostatistician (Trudy Burns); and leading hypertension physiologists (Allyn Mark, John Stokes, Robin Davisson, Gerald DiBona, and Joseph Hill) to pursue the three broad goals of the Hypertension Molecular Genetics SCOR. The strengths of the proposal include: (1) study of two distinctive human populations including nuclear families from the Muscatine population study of obesity and blood pressure; and Bedouin families from a homogenous population in Southern Israel with a high incidence of obesity; (2) a leading human and rat molecular genetics laboratory with capability for high throughput gene identification, sequencing of cDNAs, and generation and analysis of cDNA microarrays; (3) coordinated pursuit of chromosomal quantitative trait loci, physiologic and cellular intermediate phenotypes, and candidate genes in rat models of genetically salt-sensitive hypertension; (4) pursuit of functional data on the consequences of genetic variation in genes encoding the epithelial sodium channel; and (5) use of transgenic mice, tissue-specific knockout mice and mutant mouse strains to test the role of tissue-specific renin- angiotensin systems in hypertension and cardiac hypertrophy, and to study fundamental mechanisms in obesity-induced hypertension. These investigators have established vibrant collaborations within our SCOR and with investigators studying the genetics of hypertension at other institutions. This coalition of leading molecular geneticists and hypertension physiologists in the Iowa SCOR holds promise for continued substantial contribution to advancing knowledge of the molecular genetics of hypertension.

该申请建议在爱荷华大学心血管中心的高血压分子遗传学中续签专业研究中心（SCOR）。总体主题是“人类和实验动物中遗传性高血压的分子和生理机制”。这项倡议，我们在过去的18个月中一直在计划资助6个项目和一项科学核心。该中心汇集了包括杰出分子遗传学家的研究人员（Val Sheffield，Bento Soares和Curt Sigmund的爱荷华州和俄亥俄州的John Rapp）；分子生物学家（Peter Snyder和John Engelhardt）；遗传流行病学家和生物统计学家（Trudy Burns）；领先的高血压生理学家（Allyn Mark，John Stokes，Robin Davisson，Gerald Dibona和Joseph Hill）追求高血压分子遗传学SCOR的三个广泛目标。该提案的优势包括：（1）研究两个独特的人群，包括肥胖和血压研究的穆斯喀汀种群研究。来自以色列南部同质人口的贝都因人家庭肥胖很高； （2）具有高吞吐量基因鉴定，cDNA测序以及cDNA微阵列的生成和分析的能力，具有高通量基因鉴定，测序的能力； （3）在遗传性盐敏感性高血压的大鼠模型中，对染色体定量性状基因座，生理和细胞中间表型以及候选基因进行了协调的追求； （4）追求有关编码上皮钠通道基因遗传变异后果的功能数据； （5）使用转基因小鼠，组织特异性的敲除小鼠和突变小鼠菌株来测试组织特异性肾上腺素 - 血管紧张素系统在高血压和心脏肥大中的作用，并研究肥胖症诱导的高血压中的基本机制。这些研究者在我们的SCOR中建立了充满活力的合作，并与研究人员一起研究其他机构的高血压遗传学。爱荷华州SCOR中领先的分子遗传学家和高血压生理学家的联盟有望继续促进对高血压分子遗传学知识的持续贡献。