RGD Reference Report - Evidence of the Importance of Nox4 in Production of Hypertension in Dahl Salt-Sensitive Rats. - Rat Genome Database

Send us a Message



 Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap)  (beta) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer) Overgo Probe Designer
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease COVID-19 Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models PhenoMiner (Quantitative Phenotypes) Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes GERRC (Gene Editing Rat Resource Center) Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Poster Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Evidence of the Importance of Nox4 in Production of Hypertension in Dahl Salt-Sensitive Rats.

Authors: Cowley AW, JR  Yang, C  Zheleznova, NN  Staruschenko, A  Kurth, T  Rein, L  Kumar, V  Sadovnikov, K  Dayton, A  Hoffman, M  Ryan, RP  Skelton, MM  Salehpour, F  Ranji, M  Geurts, A 
Citation: Cowley AW Jr, etal., Hypertension. 2016 Feb;67(2):440-50. doi: 10.1161/HYPERTENSIONAHA.115.06280. Epub 2015 Dec 7.
RGD ID: 11085830
Pubmed: (View Article at PubMed) PMID:26644237
DOI: Full-text: DOI:10.1161/HYPERTENSIONAHA.115.06280

This study reports the consequences of knocking out NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 4 (Nox4) on the development of hypertension and kidney injury in the Dahl salt-sensitive (SS) rat. Zinc finger nuclease injection of single-cell SS embryos was used to create an 8 base-pair frame-shift deletion of Nox4, resulting in a loss of the approximately 68 kDa band in Western blot analysis of renal cortical tissue of the knock out of Nox4 in the SS rat (SS(Nox4-/-)) rats. SS(Nox4-/-) rats exhibited a significant reduction of salt-induced hypertension compared with SS rats after 21 days of 4.0% NaCl diet (134+/-5 versus 151+/-3 mm Hg in SS) and a significant reduction of albuminuria, tubular casts, and glomerular injury. Optical fluorescence 3-dimensional cryoimaging revealed significantly higher redox ratios (NADH/FAD [reduced nicotinamide adenine dinucleotide/flavin adenine dinucleotide]) in the kidneys of SS(Nox4-/-) rats even when fed the 0.4% NaCl diet, indicating greater levels of mitochondrial electron transport chain metabolic activity and reduced oxidative stress compared with SS rats. Before the development of hypertension, RNA expression levels of Nox subunits Nox2, p67(phox), and p22(phox) were found to be significantly lower (P<0.05) in SS(Nox4-/-) compared with SS rats in the renal cortex. Thus, the mutation of Nox4 seems to modify transcription of several genes in ways that contribute to the protective effects observed in the SS(Nox4-/-) rats. We conclude that the reduced renal injury and attenuated blood pressure response to high salt in the SS(Nox4-/-) rat could be the result of multiple pathways, including gene transcription, mitochondrial energetics, oxidative stress, and protein matrix production impacted by the knock out of Nox4.



Disease Annotations    
hypertension  (IMP,ISO)

Phenotype Annotations    

Phenotype Values via PhenoMiner     Click to see Annotation Detail View
Options:  View chart  |  Download data table  |  View expanded data table  |  Show All Strains Clinical Measurement

Strains with Phenominer Data Strains with phenominer data
SS-Nox4em2Mcwi-/- SS/JrHsdMcwi

Objects Annotated

Genes (Rattus norvegicus)
Nox4  (NADPH oxidase 4)
Nox4em2Mcwi  (NADPH oxidase 4; zinc finger nuclease induced mutant 2, Medical College of Wisconsin)

Genes (Mus musculus)
Nox4  (NADPH oxidase 4)

Genes (Homo sapiens)
NOX4  (NADPH oxidase 4)

Strains
SS-Nox4em2Mcwi-/-  (SS-Nox4em2Mcwi-/Nox4em2Mcwi-)


Additional Information