SORCS1 contributes to the development of renal disease in rats and humans. Physiol Genomics 2013 Aug 15;45(16):720-8
Date
06/20/2013Pubmed ID
23780848Pubmed Central ID
PMC3742914DOI
10.1152/physiolgenomics.00089.2013Scopus ID
2-s2.0-84882674017 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
Many lines of evidence demonstrate that genetic variability contributes to chronic kidney disease susceptibility in humans as well as rodent models. Little progress has been made in discovering causal kidney disease genes in humans mainly due to genetic complexity. Here, we use a minimal congenic mapping strategy in the FHH (fawn hooded hypertensive) rat to identify Sorcs1 as a novel renal disease candidate gene. We investigated the hypothesis that genetic variation in Sorcs1 influences renal disease susceptibility in both rat and human. Sorcs1 is expressed in the kidney, and knocking out this gene in a rat strain with a sensitized genome background produced increased proteinuria. In vitro knockdown of Sorcs1 in proximal tubule cells impaired protein trafficking, suggesting a mechanism for the observed proteinuria in the FHH rat. Since Sorcs1 influences renal function in the rat, we went on to test this gene in humans. We identified associations between single nucleotide polymorphisms in SORCS1 and renal function in large cohorts of European and African ancestry. The experimental data from the rat combined with association results from different ethnic groups indicates a role for SORCS1 in maintaining proper renal function.
Author List
Lazar J, O'Meara CC, Sarkis AB, Prisco SZ, Xu H, Fox CS, Chen MH, Broeckel U, Arnett DK, Moreno C, Provoost AP, Jacob HJAuthors
Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of WisconsinCaitlin C. O'Meara PhD Associate Professor in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBiological Transport
Female
Genotype
Humans
Hypertension
Kidney Diseases
Kidney Tubules, Proximal
Male
Proteinuria
Rats
Receptors, Cell Surface