Faculty Collaboration Database

Molecular networks in Dahl salt-sensitive hypertension based on transcriptome analysis of a panel of consomic rats. Physiol Genomics 2008 Jun 12;34(1):54-64

Date

04/24/2008

Pubmed ID

18430809

DOI

10.1152/physiolgenomics.00031.2008

Scopus ID

2-s2.0-47249097572 (requires institutional sign-in at Scopus site)   43 Citations

Abstract

The Dahl salt-sensitive (SS) rat is a widely used model of human salt-sensitive hypertension and renal injury. We studied the molecular networks that underlie the complex disease phenotypes in the SS model, using a design that involved two consomic rat strains that were protected from salt-induced hypertension and one that was not protected. Substitution of Brown Norway (BN) chromosome 13 or 18, but not 20, into the SS genome was found to significantly attenuate salt-induced hypertension and albuminuria. Gene expression profiles were examined in the kidneys of SS and consomic SS-13(BN), SS-18(BN), and SS-20(BN) rats with a total of 240 cDNA microarrays. The substituted chromosome was overrepresented in genes differentially expressed between a consomic strain and SS rats on a 0.4% salt diet. F5, Serpinc1, Slc19a2, and genes represented by three other expressed sequence tags (ESTs), which are located on chromosome 13, were found to be differentially expressed between SS-13(BN) and all other strains examined. Likewise, Acaa2, B4galt6, Colec12, Hsd17b4, and five other ESTs located on chromosome 18 exhibited expression patterns unique to SS-18(BN). On exposure to a 4% salt diet, there were 184 ESTs in the renal cortex and 346 in the renal medulla for which SS-13(BN) and SS-18(BN) shared one expression pattern, while SS and SS-20(BN) shared another, mirroring the phenotypic segregation among the four strains. Molecular networks that might contribute to the development of Dahl salt-sensitive hypertension and albuminuria were constructed with an approach that merged biological knowledge-driven analysis and data-driven Bayesian probabilistic analysis.

Author List

Liang M, Lee NH, Wang H, Greene AS, Kwitek AE, Kaldunski ML, Luu TV, Frank BC, Bugenhagen S, Jacob HJ, Cowley AW Jr

Authors

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin

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

Albuminuria
Animals
Chromosomes, Mammalian
Gene Expression Profiling
Gene Expression Regulation
Gene Regulatory Networks
Hypertension
Inbreeding
Oligonucleotide Array Sequence Analysis
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Reproducibility of Results
Reverse Transcriptase Polymerase Chain Reaction
Sodium Chloride, Dietary
Transcription, Genetic