Universität zu Köln

Charvet, Benjamin, Guiraud, Alexandre, Malbouyres, Marilyne, Zwolanek, Daniela, Guillon, Emilie, Bretaud, Sandrine, Monnot, Catherine ORCID: 0000-0003-1334-7348, Schulze, Joerg, Bader, Hannah L., Allard, Bruno, Koch, Manuel ORCID: 0000-0002-2962-7814 and Ruggiero, Florence (2013). Knockdown of col22a1 gene in zebrafish induces a muscular dystrophy by disruption of the myotendinous junction. Development, 140 (22). S. 4602 - 4614. CAMBRIDGE: COMPANY OF BIOLOGISTS LTD. ISSN 1477-9129

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Abstract

The myotendinous junction (MTJ) is the major site of force transfer in skeletal muscle, and defects in its structure correlate with a subset of muscular dystrophies. Col22a1 encodes the MTJ component collagen XXII, the function of which remains unknown. Here, we have cloned and characterized the zebrafish col22a1 gene and conducted morpholino-based loss-of-function studies in developing embryos. We showed that col22a1 transcripts localize at muscle ends when the MTJ forms and that COLXXII protein integrates the junctional extracellular matrix. Knockdown of COLXXII expression resulted in muscular dystrophy-like phenotype, including swimming impairment, curvature of embryo trunk/tail, strong reduction of twitch-contraction amplitude and contraction-induced muscle fiber detachment, and provoked significant activation of the survival factor Akt. Electron microscopy and immunofluorescence studies revealed that absence of COLXXII caused a strong reduction of MTJ folds and defects in myoseptal structure. These defects resulted in reduced contractile force and susceptibility of junctional extracellular matrix to rupture when subjected to repeated mechanical stress. Co-injection of sub-phenotypic doses of morpholinos against col22a1 and genes of the major muscle linkage systems showed a synergistic gene interaction between col22a1 and itga7 (a7 beta 1 integrin) that was not observed with dag1 (dystroglycan). Finally, pertinent to a conserved role in humans, the dystrophic phenotype was rescued by microinjection of recombinant human COLXXII. Our findings indicate that COLXXII contributes to the stabilization of myotendinous junctions and strengthens skeletal muscle attachments during contractile activity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Charvet, Benjamin UNSPECIFIED UNSPECIFIED UNSPECIFIED Guiraud, Alexandre UNSPECIFIED UNSPECIFIED UNSPECIFIED Malbouyres, Marilyne UNSPECIFIED UNSPECIFIED UNSPECIFIED Zwolanek, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Guillon, Emilie UNSPECIFIED UNSPECIFIED UNSPECIFIED Bretaud, Sandrine UNSPECIFIED UNSPECIFIED UNSPECIFIED Monnot, Catherine UNSPECIFIED orcid.org/0000-0003-1334-7348 UNSPECIFIED Schulze, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Bader, Hannah L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Allard, Bruno UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Manuel UNSPECIFIED orcid.org/0000-0002-2962-7814 UNSPECIFIED Ruggiero, Florence UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-471952
DOI:	10.1242/dev.096024
Journal or Publication Title:	Development
Volume:	140
Number:	22
Page Range:	S. 4602 - 4614
Date:	2013
Publisher:	COMPANY OF BIOLOGISTS LTD
Place of Publication:	CAMBRIDGE
ISSN:	1477-9129
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SKELETAL-MUSCLE; EXTRACELLULAR-MATRIX; COLLAGEN-XII; BASEMENT-MEMBRANES; CELL-MEMBRANE; INTEGRIN; MUTANT; NOTOCHORD; EMBRYOS; MODEL Multiple languages Developmental Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47195