Glcci1 Deficiency Leads to Proteinuria

• Published in: Journal of the American Society of Nephrology Vol. 22; no. 11; pp. 2037 - 2046
• Main Authors: NISHIBORI, Yukino, KATAYAMA, Kan, NORLIN, Jenny, UHLEN, Mathias, PATRAKKA, Jaakko, BETSHOLTZ, Christer, TRYGGVASON, Karl, PARIKKA, Mataleena, ODDSSON, Asmundur, NUKUI, Masatoshi, HULTENBY, Kjell, WERNERSON, Annika, BING HE, EBARASI, Lwaki, RASCHPERGER, Elisabeth
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society of Nephrology 01.11.2011
• Subjects: Animals; Basic Research; Biological and medical sciences; Cytoplasm - metabolism; Dexamethasone - pharmacology; Disease Models, Animal; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - physiology; Glucocorticoids - pharmacology; Kidney Glomerulus - abnormalities; Kidney Glomerulus - physiopathology; Male; Medical sciences; Medicin och hälsovetenskap; Mice; Mice, Inbred ICR; Nephrology. Urinary tract diseases; Oligonucleotides, Antisense - pharmacology; Podocytes - physiology; Pronephros - abnormalities; Pronephros - physiopathology; Proteinuria - metabolism; Proteinuria - pathology; Proteinuria - physiopathology; Rabbits; Receptors, Glucocorticoid - deficiency; Receptors, Glucocorticoid - genetics; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Zebrafish; Nephrology; Urinary system disease; Deficiency; Lead; Urology; Heavy metal; Proteinuria; LOCALIZES; ZEBRAFISH; NEPHRIN; GLOMERULAR TRANSCRIPTOME; GENE-EXPRESSION; PODOCIN; KIDNEY; IDENTIFICATION; CELL
• ISSN: 1046-6673; 1533-3450; 1533-3450
• DOI: 10.1681/ASN.2010111147

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.