TY - JOUR
T1 - MAGI-2 is critical for the formation and maintenance of the glomerular filtration barrier in mouse kidney
AU - Ihara, Kan Ichiro
AU - Asanuma, Katsuhiko
AU - Fukuda, Tomokazu
AU - Ohwada, Shyuichi
AU - Yoshida, Midori
AU - Nishimori, Katsuhiko
N1 - Funding Information:
Supported in part by Ministry of Education, Culture, Sports, Science and Technology of Japan Grants-in-Aid for Scientific Research 20380058 and 23380055 (K.N.) and 23591201 (K.A.).
Publisher Copyright:
Copyright © 2014 American Society for Investigative Pathology.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajpath.2014.06.019
DO - 10.1016/j.ajpath.2014.06.019
M3 - Article
C2 - 25108225
AN - SCOPUS:84907902009
SN - 0002-9440
VL - 184
SP - 2699
EP - 2708
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 10
ER -