title: Glcci1 deficiency leads to proteinuria.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Matrix Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Yukino
authors.initials: Y
authors.lastname: Nishibori
authors.forename: Kan
authors.initials: K
authors.lastname: Katayama
authors.forename: Mataleena
authors.initials: M
authors.lastname: Parikka
authors.forename: Asmundur
authors.initials: A
authors.lastname: Oddsson
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nukui
authors.forename: Kjell
authors.initials: K
authors.lastname: Hultenby
authors.forename: Annika
authors.initials: A
authors.lastname: Wernerson
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Lwaki
authors.initials: L
authors.lastname: Ebarasi
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Raschperger
authors.forename: Jenny
authors.initials: J
authors.lastname: Norlin
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.forename: Jaakko
authors.initials: J
authors.lastname: Patrakka
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
mesh_terms: D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000002:abnormalities / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D050199:Podocytes / Q000502:physiology*; D060910:Pronephros / Q000002:abnormalities / Q000503:physiopathology*; D011507:Proteinuria / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D011817:Rabbits; D011965:Receptors, Glucocorticoid / Q000172:deficiency* / Q000235:genetics; D015027:Zebrafish; D029961:Zebrafish Proteins
chemical_list: D005938:Glucocorticoids; D016376:Oligonucleotides, Antisense; D011965:Receptors, Glucocorticoid; D029961:Zebrafish Proteins; C568747:glcci1a protein, zebrafish; C568746:glucocorticoid-induced transcript 1 protein, mouse; D003907:Dexamethasone