Rieke, Johanna Magdalena, Zhang, Rong, Braun, Doreen, Yilmaz, Oeznur, Japp, Anna S., Lopes, Filipa M., Pleschka, Michael, Hilger, Alina C., Schneider, Sophia, Newman, William G., Beaman, Glenda M., Nordenskjoeld, Agneta, Ebert, Anne-Karoline, Promm, Martin, Roesch, Wolfgang H., Stein, Raimund, Hirsch, Karin, Schaefer, Frank-Mattias, Schmiedeke, Eberhard, Boemers, Thomas M., Lacher, Martin, Kluth, Dietrich, Gosemann, Jan-Hendrik, Anderberg, Magnus, Barker, Gillian, Holmdahl, Gundela, Laeckgren, Goran, Keene, David, Cervellione, Raimondo M., Giorgio, Elisa, Di Grazia, Massimo, Feitz, Wouter F. J., Marcelis, Carlo L. M., Van Rooij, Iris A. L. M., Boekenkamp, Arend, Beckers, Goedele M. A., Keegan, Catherine E., Sharma, Amit ORCID: 0000-0002-2216-5389, Dakal, Tikam Chand, Wittler, Lars, Grote, Phillip ORCID: 0000-0002-9254-1458, Zwink, Nadine, Jenetzky, Ekkehart, Brusco, Alfredo, Thiele, Holger ORCID: 0000-0002-0169-998X, Ludwig, Michael, Schweizer, Ulrich ORCID: 0000-0003-1380-4780, Woolf, Adrian S. ORCID: 0000-0001-5541-1358, Odermatt, Benjamin and Reutter, Heiko (2020). SLC20A1Is Involved in Urinary Tract and Urorectal Development. Front. Cell. Dev. Biol., 8. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2296-634X

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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: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rieke, Johanna MagdalenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, RongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braun, DoreenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yilmaz, OeznurUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Japp, Anna S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopes, Filipa M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pleschka, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hilger, Alina C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, SophiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Newman, William G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beaman, Glenda M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nordenskjoeld, AgnetaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ebert, Anne-KarolineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Promm, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roesch, Wolfgang H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stein, RaimundUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hirsch, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaefer, Frank-MattiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmiedeke, EberhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boemers, Thomas M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lacher, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kluth, DietrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gosemann, Jan-HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anderberg, MagnusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barker, GillianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holmdahl, GundelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laeckgren, GoranUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keene, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cervellione, Raimondo M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giorgio, ElisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Di Grazia, MassimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feitz, Wouter F. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marcelis, Carlo L. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van Rooij, Iris A. L. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boekenkamp, ArendUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beckers, Goedele M. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keegan, Catherine E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sharma, AmitUNSPECIFIEDorcid.org/0000-0002-2216-5389UNSPECIFIED
Dakal, Tikam ChandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wittler, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grote, PhillipUNSPECIFIEDorcid.org/0000-0002-9254-1458UNSPECIFIED
Zwink, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jenetzky, EkkehartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brusco, AlfredoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDorcid.org/0000-0002-0169-998XUNSPECIFIED
Ludwig, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schweizer, UlrichUNSPECIFIEDorcid.org/0000-0003-1380-4780UNSPECIFIED
Woolf, Adrian S.UNSPECIFIEDorcid.org/0000-0001-5541-1358UNSPECIFIED
Odermatt, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reutter, HeikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-323643
DOI: 10.3389/fcell.2020.00567
Journal or Publication Title: Front. Cell. Dev. Biol.
Volume: 8
Date: 2020
Publisher: FRONTIERS MEDIA SA
Place of Publication: LAUSANNE
ISSN: 2296-634X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CLOACAL EXSTROPHY; ZEBRAFISH; SUPPORT; GLYCINEMultiple languages
Cell Biology; Developmental BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32364

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