RGD Reference Report - Kidney failure, arterial hypertension and left ventricular hypertrophy in rats with loss of function mutation of SOD3. - Rat Genome Database

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Kidney failure, arterial hypertension and left ventricular hypertrophy in rats with loss of function mutation of SOD3.

Authors: Guo, Haipeng  Xu, Dachun  Kuroki, Marcos  Lu, Zhongbing  Xu, Xin  Geurts, Aron  Osborn, John W  Chen, Yingjie 
Citation: Guo H, etal., Free Radic Biol Med. 2020 May 20;152:787-796. doi: 10.1016/j.freeradbiomed.2020.01.023. Epub 2020 Jan 21.
RGD ID: 150573712
Pubmed: PMID:31972339   (View Abstract at PubMed)
DOI: DOI:10.1016/j.freeradbiomed.2020.01.023   (Journal Full-text)

Chronic kidney disease (CKD) poses a considerable medical and public health challenge, and the Dahl/Salt Sensitive (Dahl/SS) strain is often used for CKD study. Extracellular superoxide dismutase (SOD3) is important for removing extracellular superoxide anions and is highly expressed in renal tissue. Using a novel rat strain with loss-of-function mutation of SOD3 created by replacing glutamate 124 of SOD3 with aspartic acid (SOD3E124D rat strain), we determined the effect of SOD3 on renal function and blood pressure in Dahl/SS rats. We find that SOD3E124D rats are phenotypically indistinguishable from wild type rats through 8 weeks of age, but develop profound CKD characterized by focal necrosis and fibrosis, glomerulosclerosis, massive proteinaceous cast accumulation with tubular dilatation, interstitial fibrosis with hypertension and renal failure by 21 weeks. The SOD3E124D strain represents a unique rat model that spontaneously develops CKD in an age-dependent fashion. The finding that loss of SOD3 causes CKD indicates that extracellular oxidative stress contributes to CKD and renal failure.

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decreased superoxide dismutase level onsetIMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
glomerulosclerosis onsetIMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
heart left ventricle hypertrophy  IMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
increased circulating creatinine level onsetIMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
increased fluid intake  IMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
increased food intake  IMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
increased mean systemic arterial blood pressure onsetIMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
increased systemic arterial diastolic blood pressure onsetIMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
increased systemic arterial systolic blood pressure onsetIMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
oxidative stress onsetIMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
renal cast onsetIMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
renal fibrosis onsetIMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
renal glomerulus fibrosis onsetIMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
renal interstitial fibrosis onsetIMP 150573712; 150573712; 150573712compared to SS/JrHsdMcwiRGD 
Objects Annotated

Genes (Rattus norvegicus)
Sod3  (superoxide dismutase 3)
Sod3m1Mcwi  (superoxide dismutase 3; mutation 1, Medical College of Wisconsin)

Strains
SS-Sod3m1Mcwi  (NA)


Additional Information