Open AccessGlcci1 Deficiency Leads to Proteinuria
Author(s) -
Yukino Nishibori,
Kan Katayama,
Mataleena Parikka,
Ásmundur Oddsson,
Masatoshi Nukui,
Kjell Hultenby,
Annika Wernerson,
Bing He,
Lwaki Ebarasi,
Elisabeth Raschperger,
Jenny Norlin,
Mathias Uhlén,
Jaakko Patrakka,
Christer Betsholtz,
Karl Tryggvason
Publication year - 2011
Publication title -
journal of the american society of nephrology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 4.451
H-Index - 279
eISSN - 1533-3450
pISSN - 1046-6673
DOI - 10.1681/asn.2010111147
Subject(s) - podocyte , zebrafish , gene knockdown , biology , slit diaphragm , morpholino , glomerulus , microbiology and biotechnology , kidney , medicine , endocrinology , proteinuria , gene , genetics
Unbiased transcriptome profiling and functional genomics approaches identified glucocorticoid-induced transcript 1 (GLCCI1) as being a transcript highly specific for the glomerulus, but its role in glomerular development and disease is unknown. Here, we report that mouse glomeruli express far greater amounts of Glcci1 protein compared with the rest of the kidney. RT-PCR and Western blotting demonstrated that mouse glomerular Glcci1 is approximately 60 kD and localizes to the cytoplasm of podocytes in mature glomeruli. In the fetal kidney, intense Glcci1 expression occurs at the capillary-loop stage of glomerular development. Using gene knockdown in zebrafish with morpholinos, morphants lacking Glcci1 function had collapsed glomeruli with foot-process effacement. Permeability studies of the glomerular filtration barrier in these zebrafish morphants demonstrated a disruption of the selective glomerular permeability filter. Taken together, these data suggest that Glcci1 promotes the normal development and maintenance of podocyte structure and function.