Modelling human lower urinary tract malformations in zebrafish
Abstract 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 low...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-03-01
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| Series: | Molecular and Cellular Pediatrics |
| Online Access: | https://doi.org/10.1186/s40348-023-00156-4 |
| _version_ | 1797853749563097088 |
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| author | Caroline M. Kolvenbach Gabriel C. Dworschak Johanna M. Rieke Adrian S. Woolf Heiko Reutter Benjamin Odermatt Alina C. Hilger |
| author_facet | Caroline M. Kolvenbach Gabriel C. Dworschak Johanna M. Rieke Adrian S. Woolf Heiko Reutter Benjamin Odermatt Alina C. Hilger |
| author_sort | Caroline M. Kolvenbach |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T19:55:46Z |
| format | Article |
| id | doaj.art-dc620dcacdf24d3b958ada1a32327869 |
| institution | Directory Open Access Journal |
| issn | 2194-7791 |
| language | English |
| last_indexed | 2024-04-09T19:55:46Z |
| publishDate | 2023-03-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Molecular and Cellular Pediatrics |
| spelling | doaj.art-dc620dcacdf24d3b958ada1a323278692023-04-03T05:30:17ZengSpringerOpenMolecular and Cellular Pediatrics2194-77912023-03-011011710.1186/s40348-023-00156-4Modelling human lower urinary tract malformations in zebrafishCaroline M. Kolvenbach0Gabriel C. Dworschak1Johanna M. Rieke2Adrian S. Woolf3Heiko Reutter4Benjamin Odermatt5Alina C. Hilger6Institute of Anatomy, Medical Faculty, University of BonnInstitute of Anatomy, Medical Faculty, University of BonnDepartment of Pediatrics, Children’s Hospital Medical Center, University Hospital BonnDivision of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of ManchesterDivision of Neonatology and Pediatric Intensive Care, Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander University of Erlangen-NürnbergInstitute of Anatomy, Medical Faculty, University of BonnDepartment of Pediatrics and Adolescent Medicine, Friedrich-Alexander University of Erlangen-NürnbergAbstract 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.https://doi.org/10.1186/s40348-023-00156-4 |
| spellingShingle | Caroline M. Kolvenbach Gabriel C. Dworschak Johanna M. Rieke Adrian S. Woolf Heiko Reutter Benjamin Odermatt Alina C. Hilger Modelling human lower urinary tract malformations in zebrafish Molecular and Cellular Pediatrics |
| title | Modelling human lower urinary tract malformations in zebrafish |
| title_full | Modelling human lower urinary tract malformations in zebrafish |
| title_fullStr | Modelling human lower urinary tract malformations in zebrafish |
| title_full_unstemmed | Modelling human lower urinary tract malformations in zebrafish |
| title_short | Modelling human lower urinary tract malformations in zebrafish |
| title_sort | modelling human lower urinary tract malformations in zebrafish |
| url | https://doi.org/10.1186/s40348-023-00156-4 |
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