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

@entity1 @entity4094 @entity15029 @entity16583 @entity1413 @entity121 @entity3392
UNASSIGNED: 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 @entity1 , encoding six COLVI-chains that assemble as two 'short' (a1, a2) and one 'long' chain (theoretically any one of a3-6). In @entity1 , defects in the most widely expressed heterotrimer (a123), due to mutations in the @entity16583 -3 genes, cause a heterogeneous group of @entity4094 , collectively termed COLVI-related @entity121 . Little is known about the function(s) of the recently described a4-6 chains and no mutations have been detected yet. In this study, we characterized two novel COLVI long chains in @entity3392 that are most homologous to the @entity1 a4 chain; therefore, we named the corresponding genes col6a4a and col6a4b. These orthologues represent ancestors of the @entity1 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 @entity15029 , we modelled @entity1413 , 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 @entity3392 muscle development and may provide important clues for potential @entity1 phenotypes associated with deficiency of the recently described COLVI-chains.
