MAGI-2 is critical for the formation and maintenance of the glomerular filtration barrier in mouse kidney

Kan Ichiro Ihara, Katsuhiko Asanuma, Tomokazu Fukuda, Shyuichi Ohwada, Midori Yoshida, Katsuhiko Nishimori

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Membrane-associated guanylate kinase inverted 2 (MAGI-2) is a tight junction protein in epithelial tissues. We previously reported the detailed expression patterns of MAGI-2 in mouse tissues, including kidney podocytes, based on results obtained from Venus knock-in mice for Magi2 locus. In the present study, homozygous deletion of the Magi2 gene in mice caused neonatal lethality, which was explained by podocyte morphological abnormalities and anuria. Immunohistological analysis showed that loss of MAGI-2 function induced a significant decrease in nephrin and dendrin at the slit diaphragm of the kidney, although other components of the slit diaphragm were unchanged. Furthermore, nuclear translocation of dendrin was observed in the podocytes of the MAGI-2enull mutants, along with enhanced expression of cathepsin L, which is reported to be critical for rearrangement of the actin cytoskeleton in podocytes. Expression analysis of the null mutants showed that loss of MAGI-2 function induces abnormal expression of various types of adhesion-related molecules. The present study is the first to demonstrate that MAGI-2 has a critical role in maintaining the functional structure of the slit diaphragm and that this molecule has an essential role in the functioning of the kidney filtration barrier.

Original languageEnglish
Pages (from-to)2699-2708
Number of pages10
JournalAmerican Journal of Pathology
Volume184
Issue number10
DOIs
Publication statusPublished - 2014 Jan 1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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