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Hum Mol Genet. 2015 Dec 1;24(23):6624-39. doi: 10.1093/hmg/ddv368. Epub 2015 Sep 11.

Two novel COLVI long chains in zebrafish that are essential for muscle development.

Author information

1
Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Paris F-75013, France, Institut de Myologie, Paris F-75013, France.
2
Fish Ecophysiology Group, Ifremer, L'Houmeau F-17137, France.
3
Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Paris F-75013, France, Institut de Myologie, Paris F-75013, France, Département de Physiologie, Sorbonne Universités UPMC Paris 06, Site Pitié-Salpêtrière, Paris F-75013, France.
4
Sorbonne Universités Paris VI, UMR CNRS 1127 UPMC, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière-ICM, Paris, France and.
5
Fish Ecophysiology Group, Ifremer, L'Houmeau F-17137, France, INRA LPGP, Campus de Beaulieu, Rennes F-35042, France.
6
Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Paris F-75013, France, Institut de Myologie, Paris F-75013, France, v.allamand@institut-myologie.org.

Abstract

Collagen VI (COLVI), a protein ubiquitously expressed in connective tissues, is crucial for structural integrity, cellular adhesion, migration and survival. Six different genes are recognized in mammalians, encoding six COLVI-chains that assemble as two 'short' (α1, α2) and one 'long' chain (theoretically any one of α3-6). In humans, defects in the most widely expressed heterotrimer (α123), due to mutations in the COL6A1-3 genes, cause a heterogeneous group of neuromuscular disorders, collectively termed COLVI-related muscle disorders. Little is known about the function(s) of the recently described α4-6 chains and no mutations have been detected yet. In this study, we characterized two novel COLVI long chains in zebrafish that are most homologous to the mammalian α4 chain; therefore, we named the corresponding genes col6a4a and col6a4b. These orthologues represent ancestors of the mammalian Col6a4-6 genes. By in situ hybridization and RT-qPCR, we unveiled a distinctive expression kinetics for col6a4b, compared with the other col6a genes. Using morpholino antisense oligonucleotides targeting col6a4a, col6a4b and col6a2, we modelled partial and complete COLVI deficiency, respectively. All morphant embryos presented altered muscle structure and impaired motility. While apoptosis was not drastically increased, autophagy induction was defective in all morphants. Furthermore, motoneuron axon growth was abnormal in these morphants. Importantly, some phenotypical differences emerged between col6a4a and col6a4b morphants, suggesting only partial functional redundancy. Overall, our results further confirm the importance of COLVI in zebrafish muscle development and may provide important clues for potential human phenotypes associated with deficiency of the recently described COLVI-chains.

PMID:
26362255
DOI:
10.1093/hmg/ddv368
[Indexed for MEDLINE]

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