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A novel mouse model of phospholipase A2 receptor 1-associated membranous nephropathy mimics podocyte injury in patients.
Kidney International ( IF 19.6 ) Pub Date : 2019-11-09 , DOI: 10.1016/j.kint.2019.10.022
Catherine Meyer-Schwesinger 1 , Nicola M Tomas 2 , Silke Dehde 2 , Larissa Seifert 2 , Irm Hermans-Borgmeyer 3 , Thorsten Wiech 4 , Friedrich Koch-Nolte 5 , Tobias B Huber 2 , Gunther Zahner 2
Affiliation  

The phospholipase A2 receptor 1 (PLA2R1) is the major autoantigen in patients suffering from membranous nephropathy. To date, the lack of endogenous glomerular expression of PLA2R1 in mice and rats has impeded the establishment of PLA2R1-dependent animal models of this disease. Here, we generated a transgenic mouse line expressing murine full-length PLA2R1 in podocytes. Furthermore, expression of murine PLA2R1 did not result in any morphological disturbance as high-resolution confocal microscopy demonstrated an intact nephrin distribution with normal foot processes. Transfer of rabbit anti-mPLA2R1 antibodies to these mice induced nephrotic range proteinuria, hypercholesterolemia, and histomorphological signs of membranous nephropathy. Immunohistochemical and immunofluorescence analyses revealed enhanced staining for murine PLA2R1 in the presence of unaffected staining for murine thrombospondin type-1 domain-containing 7A in the diseased mice, resembling what is classically found in patients with PLA2R1-associated membranous nephropathy Thus, our mouse model of membranous nephropathy will allow investigation of PLA2R1-specific pathomechanisms and may help to develop and assess antigen-specific treatments in vivo.

中文翻译:

一种新型的磷脂酶 A2 受体 1 相关膜性肾病小鼠模型模拟了患者的足细胞损伤。

磷脂酶 A2 受体 1 (PLA2R1) 是膜性肾病患者的主要自身抗原。迄今为止,PLA2R1 在小鼠和大鼠中缺乏内源性肾小球表达阻碍了该疾病的 PLA2R1 依赖性动物模型的建立。在这里,我们生成了在足细胞中表达鼠全长 PLA2R1 的转基因小鼠系。此外,小鼠 PLA2R1 的表达不会导致任何形态学紊乱,因为高分辨率共聚焦显微镜显示出完整的 nephrin 分布和正常的足突。将兔抗 mPLA2R1 抗体转移至这些小鼠可诱导肾病范围蛋白尿、高胆固醇血症和膜性肾病的组织形态学征象。
更新日期:2019-11-09
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