RGD Reference Report - Molecular Networks in Dahl Salt-Sensitive Hypertension Based on Transcriptome Analysis of a Panel of Consomic Rats. - Rat Genome Database

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Molecular Networks in Dahl Salt-Sensitive Hypertension Based on Transcriptome Analysis of a Panel of Consomic Rats.

Authors: Liang, M  Lee, NH  Wang, H  Greene, AS  Kwitek, AE  Kaldunski, ML  Luu, TV  Frank, BC  Bugenhagen, S  Jacob, HJ  Cowley Jr, AW 
Citation: Liang M, etal., Physiol Genomics. 2008 Apr 22;.
RGD ID: 2292646
Pubmed: PMID:18430809   (View Abstract at PubMed)
DOI: DOI:10.1152/physiolgenomics.00031.2008   (Journal Full-text)

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 using a total of 240 cDNA microarrays. The substituted chromosome was over-represented in genes differentially expressed between a consomic strain and SS 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). Upon 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 using an approach that merged biological knowledge-driven analysis and data-driven Bayesian probabilistic analysis. Key words: genomics, systems biology, kidney, blood pressure, diet.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HSD17B4Humanhypertension  ISOHsd17b4 (Rattus norvegicus)mRNA:decreased expression:renal cortex (rat)RGD 
Hsd17b4Rathypertension  IEP mRNA:decreased expression:renal cortex (rat)RGD 
Hsd17b4Mousehypertension  ISOHsd17b4 (Rattus norvegicus)mRNA:decreased expression:renal cortex (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hsd17b4  (hydroxysteroid (17-beta) dehydrogenase 4)

Genes (Mus musculus)
Hsd17b4  (hydroxysteroid (17-beta) dehydrogenase 4)

Genes (Homo sapiens)
HSD17B4  (hydroxysteroid 17-beta dehydrogenase 4)


Additional Information