Universität zu Köln

Forte-Gomez, Helena Fabiana, Gioia, Roberta, Tonelli, Francesca, Kobbe, Birgit, Koch, Peter, Bloch, Wilhelm, Paulsson, Mats, Zaucke, Frank, Forlino, Antonella and Wagener, Raimund (2022). Structure, evolution and expression of zebrafish cartilage oligomeric matrix protein (COMP, TSP5). CRISPR-Cas mutants show a dominant phenotype in myosepta. Front. Endocrinol., 13. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-2392

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Abstract

COMP (Cartilage Oligomeric Matrix Protein), also named thrombospondin-5, is a member of the thrombospondin family of extracellular matrix proteins. It is of clinical relevance, as in humans mutations in COMP lead to chondrodysplasias. The gene encoding zebrafish Comp is located on chromosome 11 in synteny with its mammalian orthologs. Zebrafish Comp has a domain structure identical to that of tetrapod COMP and shares 74% sequence similarity with murine COMP. Zebrafish comp is expressed from 5 hours post fertilization (hpf) on, while the protein is first detectable in somites of 11 hpf embryos. During development and in adults comp is strongly expressed in myosepta, craniofacial tendon and ligaments, around ribs and vertebra, but not in its name-giving tissue cartilage. As in mammals, zebrafish Comp forms pentamers. It is easily extracted from 5 days post fertilization (dpf) whole zebrafish. The lack of Comp expression in zebrafish cartilage implies that its cartilage function evolved recently in tetrapods. The expression in tendon and myosepta may indicate a more fundamental function, as in evolutionary distant Drosophila muscle-specific adhesion to tendon cells requires thrombospondin. A sequence encoding a calcium binding motif within the first TSP type-3 repeat of zebrafish Comp was targeted by CRISPR-Cas. The heterozygous and homozygous mutant Comp zebrafish displayed a patchy irregular Comp staining in 3 dpf myosepta, indicating a dominant phenotype. Electron microscopy revealed that the endoplasmic reticulum of myosepta fibroblasts is not affected in homozygous fish. The disorganized extracellular matrix may indicate that this mutation rather interferes with extracellular matrix assembly, similar to what is seen in a subgroup of chondrodysplasia patients. The early expression and easy detection of mutant Comp in zebrafish points to the potential of using the zebrafish model for large scale screening of small molecules that can improve secretion or function of disease-associated COMP mutants.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Forte-Gomez, Helena Fabiana UNSPECIFIED UNSPECIFIED UNSPECIFIED Gioia, Roberta UNSPECIFIED UNSPECIFIED UNSPECIFIED Tonelli, Francesca UNSPECIFIED UNSPECIFIED UNSPECIFIED Kobbe, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloch, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Paulsson, Mats UNSPECIFIED UNSPECIFIED UNSPECIFIED Zaucke, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Forlino, Antonella UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagener, Raimund UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-681921
DOI:	10.3389/fendo.2022.1000662
Journal or Publication Title:	Front. Endocrinol.
Volume:	13
Date:	2022
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-2392
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DEFICIENT MICE; MOUSE MODEL; COMP; COLLAGEN; PSEUDOACHONDROPLASIA; MUTATION; OSTEOGENESIS; BINDING; IX; THROMBOSPONDIN-5 Multiple languages Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68192