ZFIN ID: ZDB-PUB-200810-38
Investigation of alpl expression and Tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development
Ohlebusch, B., Borst, A., Frankenbach, T., Klopocki, E., Jakob, F., Liedtke, D., Graser, S.
Date: 2020
Source: Scientific Reports   10: 13321 (Journal)
Registered Authors: Klopocki, Eva, Liedtke, Daniel
Keywords: none
MeSH Terms:
  • Alkaline Phosphatase/biosynthesis*
  • Alkaline Phosphatase/genetics
  • Animals
  • Disease Models, Animal
  • Gene Expression Regulation, Enzymologic*
  • Hypophosphatasia/genetics
  • Hypophosphatasia/metabolism*
  • Hypophosphatasia/pathology
  • Musculoskeletal Development*
  • Neurogenesis*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/biosynthesis*
  • Zebrafish Proteins/genetics
PubMed: 32770041 Full text @ Sci. Rep.
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.