Universität zu Köln

Ohlebusch, Barbara, Borst, Angela, Frankenbach, Tina, Klopocki, Eva, Jakob, Franz, Liedtke, Daniel ORCID: 0000-0003-0934-7169 and Graser, Stephanie (2020). Investigation of alpl expression and Tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development. Sci Rep, 10 (1). LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ohlebusch, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Borst, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED Frankenbach, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Klopocki, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Jakob, Franz UNSPECIFIED UNSPECIFIED UNSPECIFIED Liedtke, Daniel UNSPECIFIED orcid.org/0000-0003-0934-7169 UNSPECIFIED Graser, Stephanie UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-323650
DOI:	10.1038/s41598-020-70152-5
Journal or Publication Title:	Sci Rep
Volume:	10
Number:	1
Date:	2020
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NONSPECIFIC ALKALINE-PHOSPHATASE; IN-SITU HYBRIDIZATION; HYPOPHOSPHATASIA; PROMOTES; MODEL; NEUROTRANSMISSION; DIFFERENTIATION; MINERALIZATION; METABOLISM; VERTEBRATE Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32365