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.

中文翻译：

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SOD3功能丧失突变大鼠肾功能衰竭、动脉高血压和左心室肥大。

慢性肾脏病 (CKD) 对医学和公共卫生提出了相当大的挑战，而达尔/盐敏感 (Dahl/SS) 菌株通常用于 CKD 研究。细胞外超氧化物歧化酶 (SOD3) 对去除细胞外超氧化物阴离子很重要，并且在肾组织中高度表达。使用通过用天冬氨酸代替 SOD3 的谷氨酸 124 产生的具有 SOD3 功能丧失突变的新型大鼠品系（SOD3E124D 大鼠品系），我们确定了 SOD3 对 Dahl/SS 大鼠肾功能和血压的影响。我们发现 SOD3E124D 大鼠在 8 周龄前在表型上与野生型大鼠无法区分，但会发展为以局灶性坏死和纤维化、肾小球硬化、大量蛋白质管型积聚和肾小管扩张为特征的严重 CKD，间质纤维化伴高血压和肾功能衰竭 21 周。SOD3E124D 菌株代表了一种独特的大鼠模型，它以年龄依赖性方式自发发展为 CKD。SOD3 缺失导致 CKD 的发现表明细胞外氧化应激导致 CKD 和肾功能衰竭。