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Dissection of a Genetic Locus Influencing Renal Function in the Rat and its Concordance with Kidney Disease Loci on Human Chromosome 1q21.

Authors: Garrett, MR  Gunning, WT  Radecki, T  Richard, A 
Citation: Garrett MR, etal., Physiol Genomics. 2007 May 15;.
Pubmed: (View Article at PubMed) PMID:17504948
DOI: Full-text: DOI:10.1152/physiolgenomics.00001.2007

Previously, we conducted a genome scan on a population derived from the Dahl salt-sensitive hypertensive (S) and the spontaneously hypertensive rat (SHR) using urinary albumin excretion (UAE) as our primary measure of renal function. We identified 10 quantitative trait loci (QTL) linked to several renal and/or cardiovascular traits. In particular, linkage and subsequent congenic strain analysis demonstrated that the loci on chromosome 2 had a large and significant effect on UAE compared to the S rat. The present work sought to characterize the chromosome 2 congenic strain [S.SHR(2)] by conducting a time-course analysis (week 4 to 20), including evaluating additional renal parameters, histology, electron microscopy, and gene expression/ pathway analysis. Throughout the time course the congenic strain consistently maintained a three-fold reduction in UAE compared to S rats and was supported by the histological findings of significantly reduced glomerular, tubular and interstitial changes. Gene expression/pathway analysis performed at week 4, 12, and 20 revealed that pathways involved in cellular assembly and organization, cellular movement, and immune response were controlled differently between the S and congenic. Considering all the data, the chromosome 2 congenic appears to attenuate renal damage primarily through an altered fibrotic response. Recombinant progeny testing (RPT) was employed to reduce the QTL to ~ 1.5cM containing several interesting candidate genes. The concordance of this rat QTL with renal disease loci on human chromosome 1q21 demonstrate that elucidating the causative gene and mechanism of the rat QTL may be of particular importance for understanding kidney disease in humans. Key words: Dahl salt-sensitive, QTL, Proteinuria, RPT, fibrosis.


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CRRD Object Information
CRRD ID: 1625111
Created: 2007-05-22
Species: All species
Last Modified: 2007-05-22
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.