Dataset Information


Susceptibility loci for murine HIV-associated nephropathy encode trans-regulators of podocyte gene expression.

ABSTRACT: Multiple studies have linked podocyte gene variants to diverse sporadic nephropathies, including HIV-1-associated nephropathy (HIVAN). We previously used linkage analysis to identify a major HIVAN susceptibility locus in mouse, HIVAN1. We performed expression quantitative trait locus (eQTL) analysis of podocyte genes in HIV-1 transgenic mice to gain further insight into genetic susceptibility to HIVAN. In 2 independent crosses, we found that transcript levels of the podocyte gene nephrosis 2 homolog (Nphs2), were heritable and controlled by an ancestral cis-eQTL that conferred a 3-fold variation in expression and produced reactive changes in other podocyte genes. In addition, Nphs2 expression was controlled by 2 trans-eQTLs that localized to the nephropathy susceptibility intervals HIVAN1 and HIVAN2. Transregulation of podocyte genes was observed in the absence of HIV-1 or glomerulosclerosis, indicating that nephropathy susceptibility alleles induce latent perturbations in the podocyte expression network. Presence of the HIV-1 transgene interfered with transregulation, demonstrating effects of gene-environment interactions on disease. These data demonstrate that transcript levels of Nphs2 and related podocyte-expressed genes are networked and suggest that the genetic lesions introduced by HIVAN susceptibility alleles perturb this regulatory pathway and transcriptional responses to HIV-1, increasing susceptibility to nephropathy.


PROVIDER: S-EPMC2673856 | BioStudies | 2009-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC3148704 | BioStudies
2016-01-01 | S-EPMC5063463 | BioStudies
1000-01-01 | S-EPMC356977 | BioStudies
2009-01-01 | S-EPMC2753461 | BioStudies
| GSE86269 | GEO
2011-01-01 | S-EPMC3050085 | BioStudies
2019-01-01 | S-EPMC6818796 | BioStudies
1000-01-01 | S-EPMC5328167 | BioStudies
2011-01-01 | S-EPMC3231786 | BioStudies
2013-01-01 | S-EPMC3707882 | BioStudies