A Novel Mouse Model of Idiopathic Nephrotic Syndrome Induced by Immunization with the Podocyte Protein Crb2

Ichiro Hada, Akira Shimizu, Hiromu Takematsu, Yukino Nishibori, Toru Kimura, Toshiyuki Fukutomi, Akihiko Kudo, Noriko Ito-Nitta, Zentaro Kiuchi, Jaakko Patrakka, Naoaki Mikami, Simon Leclerc, Yoshihiro Akimoto, Yoshiaki Hirayama, Satoka Mori, Tomoko Takano, Kunimasa Yan

研究成果: Article査読

2 被引用数 (Scopus)


Background The cause of podocyte injury in idiopathic nephrotic syndrome (INS) remains unknown. Although recent evidence points to the role of B cells and autoimmunity, the lack of animal models mediated by autoimmunity limits further research. We aimed to establish a mouse model mimicking human INS by immunizing mice with Crb2, a transmembrane protein expressed at the podocyte foot process. Methods C3H/HeN mice were immunized with the recombinant extracellular domain of mouse Crb2. Serum anti-Crb2 antibody, urine protein-to-creatinine ratio, and kidney histology were studied. For signaling studies, a Crb2-expressing mouse podocyte line was incubated with anti-Crb2 antibody. Results Serum anti-Crb2 autoantibodies and significant proteinuria were detected 4 weeks after the first immunization. The proteinuria reached nephrotic range at 9-13 weeks and persisted up to 29 weeks. Initial kidney histology resembled minimal change disease in humans, and immunofluorescence staining showed delicate punctate IgG staining in the glomerulus, which colocalized with Crb2 at the podocyte foot process. A subset of mice developed features resembling FSGS after 18 weeks. In glomeruli of immunized mice and in Crb2-expressing podocytes incubated with anti-Crb2 antibody, phosphorylation of ezrin, which connects Crb2 to the cytoskeleton, increased, accompanied by altered Crb2 localization and actin distribution. Conclusion The results highlight the causative role of anti-Crb2 autoantibody in podocyte injury in mice. Crb2 immunization could be a useful model to study the immunologic pathogenesis of human INS, and may support the role of autoimmunity against podocyte proteins in INS.

ジャーナルJournal of the American Society of Nephrology
出版ステータスPublished - 11-2022

All Science Journal Classification (ASJC) codes

  • 腎臓病学


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