DESCRIPTION:

QTL associated with HIV-associated nephropathy 1. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (24235798)

LABEL:

QTL-Hivan1-Mouse-Chr 3

SCORE TYPE:

Binary

DATE ADDED:

2012-04-02

DATE UPDATED:

2024-04-25

SPECIES:

URI:

http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:3037874

AUTHORS:

Papeta N, Chan KT, Prakash S, Martino J, Kiryluk K, Ballard D, Bruggeman LA, Frankel R, Zheng Z, Klotman PE, Zhao H, D\'Agati VD, Lifton RP, Gharavi AG

TITLE:

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

JOURNAL:

The Journal of clinical investigation May 2009, Vol 119, pp. 1178-88

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. PUBMED: 19381020
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