Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/7194

Appears in Collections:Aquaculture Journal Articles
Peer Review Status: Refereed
Title: Developmental defects in a zebrafish model for muscular dystrophies associated with the loss of fukutin-related protein (FKRP)
Authors: Thornhill, P
Bassett, D
Lochmuller, H
Bushby, K
Straub, V
Contact Email: d.i.bassett@stir.ac.uk
Keywords: Dystroglycan
Glycosylation
Muscular dystrophy
Zebrafish
Issue Date: Jun-2008
Publisher: Oxford University Press
Citation: Thornhill P, Bassett D, Lochmuller H, Bushby K & Straub V (2008) Developmental defects in a zebrafish model for muscular dystrophies associated with the loss of fukutin-related protein (FKRP), Brain, 131 (6), pp. 1551-1561.
Abstract: A number of muscular dystrophies are associated with the defective glycosylation of alpha-dystroglycan and many are now known to result from mutations in a number of genes encoding putative or known glycosyltransferases. These diseases include severe forms of congenital muscular dystrophy (CMD) such as Fukuyama type congenital muscular dystrophy (FCMD), Muscle-Eye-Brain disease (MEB) and Walker-Warburg syndrome (WWS), which are associated with brain and eye abnormalities. The defective glycosylation of alpha-dystroglycan in these disorders leads to a failure of alpha-dystroglycan to bind to extra-cellular matrix components and previous attempts to model these disorders have shown that the generation of fukutin- and Pomt1-deficient knockout mice results in early embryonic lethality due to basement membrane defects. We have used the zebrafish as an animal model to investigate the pathological consequences of downregulating the expression of the putative glycosyltransferase gene fukutin-related protein (FKRP) on embryonic development. We have found that downregulating FKRP in the zebrafish results in embryos which develop a range of abnormalities reminiscent of the developmental defects observed in human muscular dystrophies associated with mutations in FKRP. FKRP morphant embryos showed a spectrum of phenotypic severity involving alterations in somitic structure and muscle fibre organization as well as defects in developing neuronal structures and eye morphology. The pathological phenotype was found to correlate with a reduction in alpha-dystroglycan glycosylation and reduced laminin binding. Further characterization of the developmental processes affected in FKRP morphant embryos may lead to a better understanding of the pathological spectrum observed in muscular dystrophies associated with mutations in the human FKRP gene.
Type: Journal Article
URI: http://hdl.handle.net/1893/7194
URL: http://brain.oxfordjournals.org/content/131/6/1551.long
DOI Link: http://dx.doi.org/10.1093/brain/awn078
Rights: The publisher does not allow this work to be made publicly available in this Repository. Please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author. You can only request a copy if you wish to use this work for your own research or private study.
Affiliation: Newcastle University
Aquaculture (Machrihanish)
Newcastle University
Newcastle University
Newcastle University

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