@article{8683984,
  abstract     = {{Proteoglycans are structurally and functionally diverse biomacromolecules found abundantly on cell membranes and in the extracellular matrix. They consist of a core protein linked to glycosaminoglycan chains via a tetrasaccharide linkage region. Here, we show that CRISPR/Cas9-mediated b3galt6 knock-out zebrafish, lacking galactosyltransferase II, which adds the third sugar in the linkage region, largely recapitulate the phenotypic abnormalities seen in human beta 3GalT6-deficiency disorders. These comprise craniofacial dysmorphism, generalized skeletal dysplasia, skin involvement and indications for muscle hypotonia. In-depth TEM analysis revealed disturbed collagen fibril organization as the most consistent ultrastructural characteristic throughout different affected tissues. Strikingly, despite a strong reduction in glycosaminoglycan content, as demonstrated by anion-exchange HPLC, subsequent LC-MS/MS analysis revealed a small amount of proteoglycans containing a unique linkage region consisting of only three sugars. This implies that formation of glycosaminoglycans with an immature linkage region is possible in a pathogenic context. Our study, therefore unveils a novel rescue mechanism for proteoglycan production in the absence of galactosyltransferase II, hereby opening new avenues for therapeutic intervention.}},
  articleno    = {{597857}},
  author       = {{Delbaere, Sarah and De Clercq, Adelbert and Mizumoto, Shuji and Noborn, Fredrik and Bek, Jan Willem and Alluyn, Lien and Gistelinck, Charlotte and Syx, Delfien and Salmon, Phil L. and Coucke, Paul and Larson, Göran and Yamada, Shuhei and Willaert, Andy and Malfait, Fransiska}},
  editor       = {{Bianchet, Mario Antonio}},
  issn         = {{2296-634X}},
  journal      = {{FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY}},
  keywords     = {{b3galt6,proteoglycans,zebrafish,modeling,linkage region,trisaccharide linkage region,Eherls-Danlos syndrome,BONE MATERIAL PROPERTIES,CHONDROITIN SULFATE,GALACTOSYLTRANSFERASE-II,SWIMMING PERFORMANCE,MOLECULAR-CLONING,HEPARAN-SULFATE,EXPRESSION,IDENTIFICATION,PHENOTYPE,COLLAGEN,b3galt6,zebrafish,trisaccharide linkage region,proteoglycans,linkeropathies}},
  language     = {{und}},
  pages        = {{17}},
  title        = {{b3galt6 Knock-out zebrafish recapitulate β3GalT6-deficiency disorders in human and reveal a trisaccharide proteoglycan linkage region}},
  url          = {{http://doi.org/10.3389/fcell.2020.597857}},
  volume       = {{8}},
  year         = {{2020}},
}

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