| Registro completo |
| Provedor de dados: |
ArchiMer
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| País: |
France
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| Título: |
Two novel COLVI long chains in zebrafish that are essential for muscle development
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| Autores: |
Ramanoudjame, Laetitia
Rocancourt, Claire
Laine, Jeanne
Klein, Arnaud
Joassard, Lucette
Gartioux, Corine
Fleury, Marjory
Lyphout, Laura
Kabashi, Edor
Ciura, Sorana
Cousin, Xavier
Allamand, Valerie
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| Data: |
2015-12
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| Ano: |
2015
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| Resumo: |
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.
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| Tipo: |
Text
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| Idioma: |
Inglês
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| Identificador: |
https://archimer.ifremer.fr/doc/00297/40773/46351.pdf
DOI:10.1093/hmg/ddv368
https://archimer.ifremer.fr/doc/00297/40773/
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| Editor: |
Oxford Univ Press
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| Formato: |
application/pdf
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| Fonte: |
Human Molecular Genetics (0964-6906) (Oxford Univ Press), 2015-12 , Vol. 24 , N. 23 , P. 6624-6639
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| Direitos: |
The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
info:eu-repo/semantics/openAccess
restricted use
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