|Author(s)||Ramanoudjame Laetitia1, 2, Rocancourt Claire3, Laine Jeanne1, 2, 4, Klein Arnaud1, 2, Joassard Lucette3, Gartioux Corine1, 2, Fleury Marjory1, 2, Lyphout Laura3, Kabashi Edor5, Ciura Sorana5, Cousin Xavier3, 6, Allamand Valerie1, 2|
|Affiliation(s)||1 : Univ Paris 06, Univ Paris 04, Ctr Rech Myol,UMRS974, INSERM,CNRS FRE3617, F-75651 Paris 13, France.
2 : Inst Myol, F-75013 Paris, France.
3 : IFREMER, Fish Ecophysiol Grp, F-17137 Lhoumeau, France.
4 : Univ Paris 06, Univ Paris 04, Dept Physiol, F-75013 Paris, France.
5 : Univ Paris 06, Univ Paris 04,INSERM U 1127, CNRS UMR 1127, Inst Cerveau & Moelle Epiniere ICM,UMR 7225, Paris, France.
6 : INRA LPGP, F-35042 Rennes, France.
|Source||Human Molecular Genetics (0964-6906) (Oxford Univ Press), 2015-12 , Vol. 24 , N. 23 , P. 6624-6639|
|WOS© Times Cited||12|
|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.|
Ramanoudjame Laetitia, Rocancourt Claire, Laine Jeanne, Klein Arnaud, Joassard Lucette, Gartioux Corine, Fleury Marjory, Lyphout Laura, Kabashi Edor, Ciura Sorana, Cousin Xavier, Allamand Valerie (2015). Two novel COLVI long chains in zebrafish that are essential for muscle development. Human Molecular Genetics, 24(23), 6624-6639. Publisher's official version : https://doi.org/10.1093/hmg/ddv368 , Open Access version : https://archimer.ifremer.fr/doc/00297/40773/