Faculty Collaboration Database

Interaction between Rf-1 and Rf-4 quantitative trait loci increases susceptibility to renal damage in double congenic rats. Kidney Int 2005 Dec;68(6):2462-72

Date

12/01/2005

Pubmed ID

16316323

DOI

10.1111/j.1523-1755.2005.00722.x

Scopus ID

2-s2.0-32844464712 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

BACKGROUND: Five quantitative trait loci (QTLs), Rf-1 to Rf-5, were found in Fawn-Hooded hypertensive (FHH) rats influencing susceptibility to renal damage. Previously, we found that single transfer of the Rf-1 QTL from FHH rats onto the renal-resistant August x Copenhagen Irish (ACI) strain caused a small increase in renal susceptibility. To investigate the separate role of the Rf-4 QTL and its interaction with Rf-1, we generated a single congenic strain carrying Rf-4 and a double congenic carrying both Rf-1 and Rf-4.

METHODS: Differences in renal susceptibility between ACI, Rf-1A, and Rf-4 single congenics and Rf-1A+4 double congenics were assessed using four different treatments: control (two-kidney), two-kidney with l-arginine analogue N-nitro-l-arginine methyl ester (L-NAME)-induced hypertension, unilateral nephrectomy, and unilateral nephrectomy + L-NAME. In separate experiments, renal blood flow (RBF) autoregulation was compared between two-kidney ACI and congenic rats.

RESULTS: Compared to ACI, Rf-1A rats developed more renal damage, while Rf-4 rats did not. The most severe renal damage was found in the Rf-1A+4 double congenic rats. Analysis of variance (ANOVA) demonstrated a significant interaction between the Rf-1A and Rf-4 QTLs. The magnitude of the interaction varied with the type and duration of the treatment. The RBF autoregulation was impaired in Rf-1A single and Rf-1A+4 double congenics, while in Rf-4 single congenics it was similar to that of ACI controls.

CONCLUSION: These findings indicate that the Rf-1 QTL directly influences renal susceptibility and autoregulation. In contrast, the Rf-4 QTL shows no direct effects, but significantly increases susceptibility to renal damage via an interaction with Rf-1.

Author List

Van Dijk SJ, Specht PA, Lutz MM, Lazar J, Jacob HJ, Provoost AP

MESH terms used to index this publication - Major topics in bold

Albuminuria
Animals
Animals, Congenic
Blood Pressure
Chromosomes, Mammalian
Genetic Linkage
Genetic Predisposition to Disease
Homeostasis
Homozygote
Hypertension, Renal
Quantitative Trait Loci
Rats
Rats, Inbred ACI
Renal Circulation
Specific Pathogen-Free Organisms
Survival Rate