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.
|Original language||English (US)|
|Number of pages||10|
|Journal||Free Radical Biology and Medicine|
|State||Published - May 20 2020|
Bibliographical noteFunding Information:
This study was supported by a grants from American Heart Association .
© 2020 Elsevier Inc.
- Chronic kidney disease
- Extracellular SOD
- Oxidative stress
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't