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IMMUNE AND NONIMMUNE BASES OF RENAL DISEASE

肾病的免疫和非免疫基础

基本信息

批准号：
6849715
负责人：
IEKUNI ICHIKAWA
金额：
$ 35.86万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-12-01 至 2006-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6849715
关键词：
angiotensin II angiotensin receptor congenital kidney disorder developmental genetics gene targeting introns laboratory mouse laboratory rat nucleotides perinatal receptor expression smooth muscle vertebrate embryology

项目摘要

Over the last 15 years, the PI's effort to investigate the 'immune and non-immune mechanisms of renal diseases' has progressively focused on the role of the renin-angiotensin system (RAS). Through animal and human studies, the PT has documented that angiotensin II produces damages to the kidney through several previously recognized and unrecognized biological properties. In an attempt to pinpoint the specific biological events involved in the actions of angiotensin II, the PI took the step to completely and selectively inactivate the several genes comprising RAS, i.e., the genes of its precursor, metabolizing enzyme and receptors. From the early stage of analyzing the produced mutants, however, the PI began to realize that RAS has an important physiological role for the ontogeny of the kidney and urinary tract, and that, in fact, a defect in this system, can cause diseases of the kidney and urinary tract. A mutation in one of those genes has even been linked to a special group of common (1 / 100 births) congenital human diseases, which are collectively called 'congenital anomalies of the kidney and urinary tract'. Taking this newly arrived opportunity, the PI now plans to delineate the ontogeny of this disease entity, and at the same time, to shed light into the physiologic role of RAS in normal kidney and urinary tract development.

在过去的15年里，PI致力于调查“免疫” 和非免疫机制的肾脏疾病“已逐步集中在肾素-血管紧张素系统（RAS）。通过动物和人类研究， PT记录了血管紧张素II对肾脏的损害通过几个以前认识到和未认识到的生物学特性。在试图确定特定的生物学事件涉及的血管紧张素II的作用，PI采取步骤，完全和选择性地包括RAS的几个基因，即，其前体的基因，代谢酶和受体。然而，从分析产生的突变体的早期阶段开始，PI开始认识到RAS在个体发育中具有重要的生理作用，肾脏和泌尿道，事实上，这个系统的缺陷，会导致肾脏和泌尿道疾病。其中一个基因的突变甚至与一组特殊的常见（1 / 100出生）先天性人类这些疾病统称为“先天性肾脏异常”，泌尿道利用这个新的机会，PI现在计划描述这种疾病实体的个体发育，同时，阐明RAS在正常肾脏和泌尿道中的生理作用发展