Investigation of alpl expression and Tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development
Please always quote using this URN: urn:nbn:de:bvb:20-opus-230024
- Hypophosphatasia (HPP) is a rare genetic disease with diverse symptoms and a heterogeneous severity of onset with underlying mutations in the ALPL gene encoding the ectoenzyme Tissue-nonspecific alkaline phosphatase (TNAP). Considering the establishment of zebrafish (Danio rerio) as a new model organism for HPP, the aim of the study was the spatial and temporal analysis of alpl expression in embryos and adult brains. Additionally, we determined functional consequences of Tnap inhibition on neural and skeletal development in zebrafish. We showHypophosphatasia (HPP) is a rare genetic disease with diverse symptoms and a heterogeneous severity of onset with underlying mutations in the ALPL gene encoding the ectoenzyme Tissue-nonspecific alkaline phosphatase (TNAP). Considering the establishment of zebrafish (Danio rerio) as a new model organism for HPP, the aim of the study was the spatial and temporal analysis of alpl expression in embryos and adult brains. Additionally, we determined functional consequences of Tnap inhibition on neural and skeletal development in zebrafish. We show that expression of alpl is present during embryonic stages and in adult neuronal tissues. Analyses of enzyme function reveal zones of pronounced Tnap-activity within the telencephalon and the mesencephalon. Treatment of zebrafish embryos with chemical Tnap inhibitors followed by axonal and cartilage/mineralized tissue staining imply functional consequences of Tnap deficiency on neuronal and skeletal development. Based on the results from neuronal and skeletal tissue analyses, which demonstrate an evolutionary conserved role of this enzyme, we consider zebrafish as a promising species for modeling HPP in order to discover new potential therapy strategies in the long-term.…
Author: | Barbara Ohlebusch, Angela Borst, Tina Frankenbach, Eva KlopockiORCiD, Franz JakobORCiD, Daniel LiedtkeORCiD, Stephanie GraserORCiD |
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URN: | urn:nbn:de:bvb:20-opus-230024 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Institut für Humangenetik |
Medizinische Fakultät / Lehrstuhl für Orthopädie | |
Language: | English |
Parent Title (English): | Scientific Reports |
Year of Completion: | 2020 |
Volume: | 10 |
Article Number: | 13321 |
Source: | Scientific Reports (2020) 10:13321. https://doi.org/10.1038/s41598-020-70152-5 |
DOI: | https://doi.org/10.1038/s41598-020-70152-5 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | differentiation; hypophosphatasia; in situ hybridization; metabolism; mineraliztion; model; neurotransmission; nonspecific alkaline-phosphae; promotes; vertebrate |
Release Date: | 2021/04/19 |
Open-Access-Publikationsfonds / Förderzeitraum 2020 | |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |