Genetic Analysis of Renal Disease in SHR and Dahl S Rats

SHR 和 Dahl S 大鼠肾病的遗传分析

• 批准号: 6637544
• 负责人: MICHAEL R GARRETT
• 金额: $ 25.73万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-08 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6637544
• 关键词: animal breeding; animal population genetics; blood pressure; chronic renal failure; genetic strain; genetic susceptibility; hypertension; laboratory rat; linkage mapping; proteinuria; quantitative trait loci; spontaneous hypertensive rat

DESCRIPTION (Verbatim from the application): End stage renal disease (ESRD) in humans is an important medical problem requiring the expensive treatments of dialysis and renal transplantation. Studies in humans suggest that ESRO has a complex genetic component. In order to understand the genetic causes of ESRD we propose to define the genetic components responsible for the development of the rapidly progressing renal pathology in the Dahi salt sensitive (S) rat. To do this, segregating populations derived from crossing S rats with spontaneously hypertensive rats (SHR) will be studied. The two strains are markedly different with regard to proteinuria and progression of renal disease. Young S rats have very high proteinuria and rapidly develop renal lesions; young SHR show essentially minimal proteinuria and very slow progression of renal disease in spite of their high blood pressure. Linkage analysis for the quantitative trait loci (QTL) controlling the marked difference in proteinuria between S and SHR will be performed starting at a young age and also at successive time points in an F2(SHR X S) population fed a low salt diet to minimize the development of hypertension. The QTL for blood pressure that differentiate S and SHR rats have already been defined on high salt diet as residing on rat chromosomes 3, 6, 8 and 9. The relationship of these blood pressure QTL to the QTL for progressive proteinuria/renal disease will be sought by determining the positions of the QTL for both traits in an F2(SHR X S) population fed high salt diet. One of the blood pressure QTL differentiating S and SHR is likely to be related to the marked difference in the vascular smooth muscle response between S and SHR to ionic cobalt. This is a Mendelian trait and it will be placed on the rat genetic map to determine its relationship to blood pressure and proteinuria QTL. Lastly, the development of congenic strains will be initiated for any unique QTL, especially those for proteinuria/renal disease, defined by the above genetic analysis. These congenic strains are required for later fine genetic mapping and ultimate gene identification.

描述（来自申请）：终末期肾脏疾病（ESRD）

项目成果

Investigating the effect of genetic background on proteinuria and renal injury using two hypertensive strains.

使用两种高血压菌株研究遗传背景对蛋白尿和肾损伤的影响。

• DOI: 10.1152/ajprenal.90370.2008
• 发表时间: 2009
• 期刊: American journal of physiology. Renal physiology
• 作者: Packard,Matthew;Saad,Yasser;Gunning,WilliamT;Gupta,Shalini;Shapiro,Joseph;Garrett,MichaelR
• 通讯作者: Garrett,MichaelR