Modelling human lower urinary tract malformations in zebrafish.

Autor: Kolvenbach CM; Institute of Anatomy, Medical Faculty, University of Bonn, Bonn, Germany. Caroline.Kolvenbach@gmail.com.; Division of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Caroline.Kolvenbach@gmail.com., Dworschak GC; Institute of Anatomy, Medical Faculty, University of Bonn, Bonn, Germany.; Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.; Department of Neuropediatrics, University Hospital Bonn, Bonn, Germany., Rieke JM; Department of Pediatrics, Children's Hospital Medical Center, University Hospital Bonn, Bonn, Germany., Woolf AS; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK.; Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Reutter H; Division of Neonatology and Pediatric Intensive Care, Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany., Odermatt B; Institute of Anatomy, Medical Faculty, University of Bonn, Bonn, Germany., Hilger AC; Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.; Research Center On Rare Kidney Diseases (RECORD), University Hospital Erlangen, Erlangen, Germany.
Jazyk: angličtina
Zdroj: Molecular and cellular pediatrics [Mol Cell Pediatr] 2023 Mar 29; Vol. 10 (1), pp. 2. Date of Electronic Publication: 2023 Mar 29.
DOI: 10.1186/s40348-023-00156-4
Abstrakt: Advances in molecular biology are improving our understanding of the genetic causes underlying human congenital lower urinary tract (i.e., bladder and urethral) malformations. This has recently led to the identification of the first disease-causing variants in the gene BNC2 for isolated lower urinary tract anatomical obstruction (LUTO), and of WNT3 and SLC20A1 as genes implicated in the pathogenesis of the group of conditions called bladder-exstrophy-epispadias complex (BEEC). Implicating candidate genes from human genetic data requires evidence of their influence on lower urinary tract development and evidence of the found genetic variants' pathogenicity. The zebrafish (Danio rerio) has many advantages for use as a vertebrate model organism for the lower urinary tract. Rapid reproduction with numerous offspring, comparable anatomical kidney and lower urinary tract homology, and easy genetic manipulability by Morpholino®-based knockdown or CRISPR/Cas editing are among its advantages. In addition, established marker staining for well-known molecules involved in urinary tract development using whole-mount in situ hybridization (WISH) and the usage of transgenic lines expressing fluorescent protein under a tissue-specific promoter allow easy visualization of phenotypic abnormalities of genetically modified zebrafish. Assays to examine the functionality of the excretory organs can also be modeled in vivo with the zebrafish. The approach of using these multiple techniques in zebrafish not only enables rapid and efficient investigation of candidate genes for lower urinary tract malformations derived from human data, but also cautiously allows transferability of causality from a non-mammalian vertebrate to humans.
(© 2023. The Author(s).)
Databáze: MEDLINE
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