TY  - JOUR
A1  - Ohlebusch, Barbara
A1  - Borst, Angela
A1  - Frankenbach, Tina
A1  - Klopocki, Eva
A1  - Jakob, Franz
A1  - Liedtke, Daniel
A1  - Graser, Stephanie
T1  - Investigation of alpl expression and Tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development
T2  - Scientific Reports
N2  - 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 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.
KW  - nonspecific alkaline-phosphae
KW  - in situ hybridization
KW  - hypophosphatasia
KW  - promotes
KW  - model
KW  - neurotransmission
KW  - differentiation
KW  - mineraliztion
KW  - metabolism
KW  - vertebrate
Y1  - 2020
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/23002
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-230024
VL  - 10
ER  -