title: Molecular networks in Dahl salt-sensitive hypertension based on transcriptome analysis of a panel of consomic rats.
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.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. mliang@mcw.edu
authors.forename: Mingyu
authors.initials: M
authors.lastname: Liang
authors.forename: Norman H
authors.initials: NH
authors.lastname: Lee
authors.forename: Hongying
authors.initials: H
authors.lastname: Wang
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greene
authors.forename: Anne E
authors.initials: AE
authors.lastname: Kwitek
authors.forename: Mary L
authors.initials: ML
authors.lastname: Kaldunski
authors.forename: Truong V
authors.initials: TV
authors.lastname: Luu
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Frank
authors.forename: Scott
authors.initials: S
authors.lastname: Bugenhagen
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Jacob
authors.forename: Allen W
authors.initials: AW
authors.lastname: Cowley
mesh_terms: D000419:Albuminuria / Q000235:genetics; D000818:Animals; D033481:Chromosomes, Mammalian / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks; D006973:Hypertension / Q000235:genetics*; D007178:Inbreeding; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D014158:Transcription, Genetic
chemical_list: D017673:Sodium Chloride, Dietary