New Anti-Nephrin Antibody Mediated Podocyte Injury Model Using a C57BL/6 Mouse Strain
New Anti-Nephrin Antibody Mediated Podocyte Injury Model Using a C57BL/6 Mouse Strain
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DOI：
10.1159/000479935
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发表时间：
2018-01-01
期刊：
影响因子：
2.5
通讯作者：
Takeuchi, Yasuo
中科院分区：
文献类型：
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作者：
Takeuchi, Kazuhiro;Naito, Shokichi;Takeuchi, Yasuo
背景：局灶节段性肾小球硬化症（FSGS）被认为是足细胞病的一个子集。足细胞病的分子发病机制仍不清楚。目前广泛采用的C57BL/6株抗体诱导分离足细胞病的实验动物模型尚未见报道。去氧肾上腺素与肾小球足细胞的裂隙隔膜密切相关，最近作为潜在的治疗靶点受到关注。去氧肾上腺素的功能，特别是其通过足细胞病在 FSGS 发展中的作用正在被阐明。我们报告了由多克隆兔抗小鼠去氧肾上腺素抗体（α-mNep Ab）诱导的 C57BL/6 FSGS 模型的经验。方法：将基因免疫产生的α-mNep Ab一次性静脉注射给C57BL/6小鼠。评估尿蛋白排泄、肾小球硬化的发展和小鼠肾脏中足细胞的数量。结果：α-mNep Ab 诱导的 FSGS 与大量蛋白尿和肾病综合征相关。在高碘酸希夫染色中，从抗体注射后第7天开始观察到FSGS。足细胞数量和足细胞标记物（抗肾母细胞瘤1和抗突触蛋白）阳性面积明显减少。这些结果表明该 FSGS 小鼠模型可靠地再现了人类肾病综合征和 FSGS。结论：我们利用C57BL/6成功制作了α-mNep Ab诱导的肾病综合征模型小鼠。该模型可能有助于研究足细胞病的机制。 (C) 2017 S. Karger AG，巴塞尔
Background: Focal segmental glomerulosclerosis (FSGS) is considered a subset of the podocytopathies. The molecular pathogenesis of podocytopathy is still unknown. There has not been an experimental animal model of isolated podocytopathy induced by antibody in C57BL/6 strain, which is widely used as the genetic background. Nephrin is closely associated with the slit diaphragm of the glomerular podocyte, and has recently received attention as a potential therapeutic target. The function of nephrin, especially its role in FSGS development via podocytopathy, is being elucidated. We report our experience with a C57BL/6 FSGS model induced by polyclonal rabbit anti-mouse nephrin antibody (alpha-mNep Ab). Methods: alpha-mNep Ab, which was generated by genetic immunization, was administered into C57BL/6 mice at once, intravenously. Urinary protein excretion, the development of glomerulosclerosis and the number of podocyte in mouse kidney were evaluated. Results: The alpha-mNep Ab-induced FSGS was associated with massive proteinuria and nephrotic syndrome. In periodic acid-Schiff staining, FSGS was observed from day 7 after antibody injection. Podocyte numbers and podocyte marker (anti-Wilms tumor 1 and anti-synaptopodin)-positive areas were clearly decreased. These results suggest that this FSGS mouse model reliably reproduces the human nephrotic syndrome and FSGS. Conclusion: We succeeded in making the nephrotic syndrome model mice induced by alpha-mNep Ab using C57BL/6. This model may be useful for studying the mechanisms of podocytopathy. (C) 2017 S. Karger AG, Basel