Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Analysis of the genomic architecture of a complex trait locus in hypertensive rat models links Tmem63c to kidney damage

[img]
Preview
PDF (Accepted Manuscript) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
6MB
[img] Other (Additional Files)
114MB

Item Type:Article
Title:Analysis of the genomic architecture of a complex trait locus in hypertensive rat models links Tmem63c to kidney damage
Creators Name:Schulz, A. and Müller, N.V. and van de Lest, N.A. and Eisenreich, A. and Schmidbauer, M. and Barysenka, A. and Purfürst, B. and Sporbert, A. and Lorenzen, T. and Meyer, A.M. and Herlan, L. and Witten, A. and Rühle, F. and Zhou, W. and de Heer, E. and Scharpfenecker, M. and Panáková, D. and Stoll, M. and Kreutz, R.
Abstract:Unraveling the genetic susceptibility of complex diseases such as chronic kidney disease remains challenging. Here, we used inbred rat models of kidney damage associated with elevated blood pressure for the comprehensive analysis of a major albuminuria susceptibility locus detected in these models. We characterized its genomic architecture by congenic substitution mapping, targeted next generation sequencing, and compartment-specific RNA sequencing analysis in isolated glomeruli. This led to prioritization of transmembrane protein Tmem63c as a novel potential target. Tmem63c is differentially expressed in glomeruli of allele-specific rat models during onset of albuminuria. Patients with focal segmental glomerulosclerosis exhibited specific TMEM63C loss in podocytes. Functional analysis in zebrafish revealed a role for tmem63c in mediating the glomerular filtration barrier function. Our data demonstrate that integrative analysis of the genomic architecture of a complex trait locus is a powerful tool for identification of new targets such as Tmem63c for further translational investigation.
Keywords:Animals, Rats, Zebrafish
Source:eLife
ISSN:2050-084X
Publisher:eLife Sciences Publications (U.K.)
Volume:8
Page Range:e42068
Date:22 March 2019
Official Publication:https://doi.org/10.7554/eLife.42068
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library