SLC20A1 Is Involved in Urinary Tract and Urorectal Development

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Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as 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 of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. 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 detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, 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 suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC.


  • Johanna Magdalena Rieke
  • Rong Zhang
  • Doreen Braun
  • Öznur Yilmaz
  • Anna S. Japp
  • Filipa M. Lopes
  • Michael Pleschka
  • Alina C. Hilger
  • Sophia Schneider
  • William G. Newman
  • Glenda M. Beaman
  • Agneta Nordenskjöld
  • Anne Karoline Ebert
  • Martin Promm
  • Wolfgang H. Rösch
  • Raimund Stein
  • Karin Hirsch
  • Frank Mattias Schäfer
  • Eberhard Schmiedeke
  • Thomas M. Boemers
  • Martin Lacher
  • Dietrich Kluth
  • Jan Hendrik Gosemann
  • Gillian Barker
  • Gundela Holmdahl
  • Göran Läckgren
  • David Keene
  • Raimondo M. Cervellione
  • Elisa Giorgio
  • Massimo Di Grazia
  • Wouter F.J. Feitz
  • Carlo L.M. Marcelis
  • Iris A.L.M. Van Rooij
  • Arend Bökenkamp
  • Goedele M.A. Beckers
  • Catherine E. Keegan
  • Amit Sharma
  • Tikam Chand Dakal
  • Lars Wittler
  • Phillip Grote
  • Nadine Zwink
  • Ekkehart Jenetzky
  • Alfredo Brusco
  • Holger Thiele
  • Michael Ludwig
  • Ulrich Schweizer
  • Adrian S. Woolf
  • Benjamin Odermatt
  • Heiko Reutter
Externa organisationer
  • Universitätsklinikum Bonn
  • Universitätsklinikum Düsseldorf
  • Central Manchester University Hospitals
  • Karolinska Institute
  • Karolinska University Hospital
  • University Hospital of Ulm
  • University Hospital Regensburg
  • Heidelberg University
  • Friedrich-Alexander University Erlangen-Nürnberg
  • Klinikum Bremen-Mitte
  • Leipzig University
  • Skåne University Hospital
  • Uppsala University Hospital
  • Royal Manchester Children's Hospital
  • Citta' della Salute e della Scienza Hospital-University of Turin
  • Istituto Nazionale dei Tumori
  • Radboud University Medical Center
  • Academic Medical Center
  • University of Michigan
  • Max Planck Institute for Molecular Genetics
  • Goethe University
  • Universitätsmedizin Mainz
  • Witten/Herdecke University
  • University of Cologne
  • University of Bonn
  • University of Manchester
  • The Cnopfsche Children's Hospital
  • University Hospital of Cologne
  • Queen Silvia Children’s Hospital
  • Mohanlal Sukhadia University

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Urologi och njurmedicin


TidskriftFrontiers in cell and developmental biology
StatusPublished - 2020
Peer review utfördJa
Externt publiceradJa