SLC20A1 Is Involved in Urinary Tract and Urorectal Development.

Autor:	Rieke JM; Institute of Human Genetics, University Hospital Bonn, Bonn, Germany.; Institute for Anatomy and Cell Biology, University Hospital Bonn, University of Bonn, Bonn, Germany.; Department of Pediatrics, Children's Hospital Medical Center, University Hospital Bonn, Bonn, Germany., Zhang R; Institut für Biochemie und Molekularbiologie, Universitätsklinikum Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany., Braun D; Institute of Human Genetics, University Hospital Bonn, Bonn, Germany., Yilmaz Ö; Institute for Anatomy and Cell Biology, University Hospital Bonn, University of Bonn, Bonn, Germany., Japp AS; Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany.; Institute of Pathology, University Hospital Düsseldorf, Düsseldorf, Germany., Lopes FM; Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom., Pleschka M; Institute of Human Genetics, University Hospital Bonn, Bonn, Germany.; Institute for Anatomy and Cell Biology, University Hospital Bonn, University of Bonn, Bonn, Germany., Hilger AC; Institute of Human Genetics, University Hospital Bonn, Bonn, Germany.; Department of Pediatrics, Children's Hospital Medical Center, University Hospital Bonn, Bonn, Germany., Schneider S; Institute of Human Genetics, University Hospital Bonn, Bonn, Germany.; Department of Neonatology and Pediatric Intensive Care, Children's Hospital Medical Center, University Hospital Bonn, Bonn, Germany., Newman WG; Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom., Beaman GM; Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom., Nordenskjöld A; Department of Women's and Children's Health, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.; Pediatric Surgery, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden., Ebert AK; Department of Urology and Pediatric Urology, University Hospital of Ulm, Ulm, Germany., Promm M; Department of Pediatric Urology, Clinic St. Hedwig, University Medical Center Regensburg, Regensburg, Germany., Rösch WH; Department of Pediatric Urology, Clinic St. Hedwig, University Medical Center Regensburg, Regensburg, Germany., Stein R; Medical Faculty Mannheim, Centre for Pediatric, Adolescent and Reconstructive Urology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany., Hirsch K; Division of Pediatric Urology, Department of Urology, University of Erlangen-Nürnberg, Erlangen, Germany., Schäfer FM; Department of Pediatric Surgery and Urology, Cnopfsche Kinderklinik, Nürnberg, Germany., Schmiedeke E; Department of Pediatric Surgery and Urology, Center for Child and Youth Health, Klinikum Bremen-Mitte, Bremen, Germany., Boemers TM; Department of Pediatric Surgery and Pediatric Urology, Children's Hospital of Cologne, Cologne, Germany., Lacher M; Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany., Kluth D; Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany., Gosemann JH; Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany., Anderberg M; Department of Pediatric Surgery, Skane University Hospital Lund, Lund, Sweden., Barker G; Department of Women's and Children's Health, Uppsala Academic Children Hospital, Uppsala, Sweden., Holmdahl G; Department of Pediatric Surgery, Queen Silvias Children's Hospital, Gothenburg, Sweden., Läckgren G; Pediatric Urology, University Children's Hospital, Uppsala, Sweden., Keene D; Pediatric Urology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom., Cervellione RM; Pediatric Urology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom., Giorgio E; Department of Medical Sciences, University of Torino, Turin, Italy.; Medical Genetics Unit, Città della Salute e della Scienza University Hospital, Turin, Italy., Di Grazia M; Pediatric Urology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy., Feitz WFJ; Division of Pediatric Urology, Department of Urology, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands., Marcelis CLM; Department of Genetics, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands., Van Rooij IALM; Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands., Bökenkamp A; Emma Children's Hospital, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Beckers GMA; Department of Urology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Keegan CE; Division of Genetics, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States.; Department of Human Genetics, University of Michigan, Ann Arbor, MI, United States., Sharma A; Department of Neurology, University Hospital Bonn, Bonn, Germany.; Department of Ophthalmology, University Hospital Bonn, Bonn, Germany., Dakal TC; Department of Biotechnology, Mohanlal Sukhadia University Udaipur, Udaipur, India., Wittler L; Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany., Grote P; Institute of Cardiovascular Regeneration, Center for Molecular Medicine, Goethe University, Frankfurt am Main, Germany., Zwink N; Department of Pediatric and Adolescent Psychiatry and Psychotherapy, University Medical Centre, Johannes Gutenberg University of Mainz, Mainz, Germany., Jenetzky E; Department of Pediatric and Adolescent Psychiatry and Psychotherapy, University Medical Centre, Johannes Gutenberg University of Mainz, Mainz, Germany.; Institute of Integrative Medicine, Witten/Herdecke University, Herdecke, Germany., Brusco A; Department of Medical Sciences, University of Torino, Turin, Italy.; Medical Genetics Unit, Città della Salute e della Scienza University Hospital, Turin, Italy., Thiele H; Cologne Center for Genomics, University of Cologne, Cologne, Germany., Ludwig M; Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany., Schweizer U; Institut für Biochemie und Molekularbiologie, Universitätsklinikum Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany., Woolf AS; Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom.; Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom., Odermatt B; Institute for Anatomy and Cell Biology, University Hospital Bonn, University of Bonn, Bonn, Germany.; Institute for Neuroanatomy, University Hospital Bonn, University of Bonn, Bonn, Germany., Reutter H; Institute of Human Genetics, University Hospital Bonn, Bonn, Germany.; Department of Neonatology and Pediatric Intensive Care, Children's Hospital Medical Center, University Hospital Bonn, Bonn, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2020 Aug 07; Vol. 8, pp. 567. Date of Electronic Publication: 2020 Aug 07 (Print Publication: 2020).
DOI:	10.3389/fcell.2020.00567
Abstrakt:	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. (Copyright © 2020 Rieke, Zhang, Braun, Yilmaz, Japp, Lopes, Pleschka, Hilger, Schneider, Newman, Beaman, Nordenskjöld, Ebert, Promm, Rösch, Stein, Hirsch, Schäfer, Schmiedeke, Boemers, Lacher, Kluth, Gosemann, Anderberg, Barker, Holmdahl, Läckgren, Keene, Cervellione, Giorgio, Di Grazia, Feitz, Marcelis, Van Rooij, Bökenkamp, Beckers, Keegan, Sharma, Dakal, Wittler, Grote, Zwink, Jenetzky, Brusco, Thiele, Ludwig, Schweizer, Woolf, Odermatt and Reutter.)
Databáze:	MEDLINE
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