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b3galt6 Knock-Out Z...
b3galt6 Knock-Out Zebrafish Recapitulate beta 3GalT6-Deficiency Disorders in Human and Reveal a Trisaccharide Proteoglycan Linkage Region
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Delbaere, S. (author)
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De Clercq, A. (author)
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Mizumoto, S. (author)
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- Noborn, Fredrik (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
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Bek, J. W. (author)
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Alluyn, L. (author)
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Gistelinck, C. (author)
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Syx, D. (author)
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Salmon, P. L. (author)
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Coucke, P. J. (author)
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- Larson, Göran, 1953 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
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Yamada, S. (author)
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Willaert, A. (author)
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Malfait, F. (author)
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(creator_code:org_t)
- 2020-12-10
- 2020
- English.
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In: Frontiers in Cell and Developmental Biology. - : Frontiers Media SA. - 2296-634X. ; 8
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Utvecklingsbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Developmental Biology (hsv//eng)
Keyword
- b3galt6
- zebrafish
- trisaccharide linkage region
- proteoglycans
- linkeropathies
- bone material properties
- chondroitin sulfate
- galactosyltransferase-ii
- swimming performance
- molecular-cloning
- heparan-sulfate
- expression
- identification
- phenotype
- collagen
- Cell Biology
- Developmental Biology
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Delbaere, S.
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De Clercq, A.
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Mizumoto, S.
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Noborn, Fredrik
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Bek, J. W.
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Alluyn, L.
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show more...
-
Gistelinck, C.
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Syx, D.
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Salmon, P. L.
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Coucke, P. J.
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Larson, Göran, 1 ...
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Yamada, S.
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Willaert, A.
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Malfait, F.
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Developmental Bi ...
- Articles in the publication
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Frontiers in Cel ...
- By the university
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University of Gothenburg