Rieke, Johanna Magdalena and Zhang, Rong and Braun, Doreen and Yilmaz, Oeznur and Japp, Anna S. and Lopes, Filipa M. and Pleschka, Michael and Hilger, Alina C. and Schneider, Sophia and Newman, William G. and Beaman, Glenda M. and Nordenskjoeld, Agneta and Ebert, Anne-Karoline and Promm, Martin and Roesch, Wolfgang H. and Stein, Raimund and Hirsch, Karin and Schaefer, Frank-Mattias and Schmiedeke, Eberhard and Boemers, Thomas M. and Lacher, Martin and Kluth, Dietrich and Gosemann, Jan-Hendrik and Anderberg, Magnus and Barker, Gillian and Holmdahl, Gundela and Laeckgren, Goran and Keene, David and Cervellione, Raimondo M. and Giorgio, Elisa and Di Grazia, Massimo and Feitz, Wouter F. J. and Marcelis, Carlo L. M. and Van Rooij, Iris A. L. M. and Boekenkamp, Arend and Beckers, Goedele M. A. and Keegan, Catherine E. and Sharma, Amit and Dakal, Tikam Chand and Wittler, Lars and Grote, Phillip and Zwink, Nadine and Jenetzky, Ekkehart and Brusco, Alfredo and Thiele, Holger and Ludwig, Michael and Schweizer, Ulrich and Woolf, Adrian S. and Odermatt, Benjamin and Reutter, Heiko (2020) SLC20A1Is Involved in Urinary Tract and Urorectal Development. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 8: 567. ISSN 2296-634X,
Full text not available from this repository. (Request a copy)Abstract
Previous studies in developingXenopusand zebrafish reported that the phosphate transporterslc20a1ais expressed in pronephric kidneys. The recent identification ofSLC20A1as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role ofSLC20A1in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish orthologslc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detectedSLC20A1in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequencedSLC20A1in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelicde novovariants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novelde novovariant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact ofSLC20A1variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggestSLC20A1is involved in urinary tract and urorectal development and implicateSLC20A1as a disease-gene for BEEC.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CLOACAL EXSTROPHY; ZEBRAFISH; SUPPORT; GLYCINE; urinary tract development; kidney formation; zebrafish development; cloacal malformation; functional genetics; CAKUT; bladder exstrophy-epispadias complex |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Mar 2021 09:22 |
| Last Modified: | 16 Mar 2021 09:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44042 |
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