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    Brain dystrophin-glycoprotein complex: persistent expression of beta-dystroglycan, impaired oligomerization of Dp71 and up-regulation of utrophins in animal models of muscular dystrophy


    Culligan, Kevin and Glover, Louise and Dowling, Paul and Ohlendieck, Kay (2001) Brain dystrophin-glycoprotein complex: persistent expression of beta-dystroglycan, impaired oligomerization of Dp71 and up-regulation of utrophins in animal models of muscular dystrophy. BMC Cell Biology, 2 (2). ISSN 1471-2121

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    Official URL: http://www.biomedcentral.com/1471-2121/2/2


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    Abstract

    Background: Aside from muscle, brain is also a major expression site for dystrophin, the protein whose abnormal expression is responsible for Duchenne muscular dystrophy. Cognitive impairments are frequently associated with this genetic disease, we therefore studied the fate of brain and skeletal muscle dystrophins and dystroglycans in dystrophic animal models. Results: All dystrophin-associated glycoproteins investigated were reduced in dystrophic muscle fibres. In Dp427-deficient mdx brain and Dp71-deficient mdx-3cv brain, the expression of α- dystroglycan and laminin was reduced, utrophin isoforms were up-regulated and β-dystroglycan was not affected. Immunofluorescence localization of β-dystroglycan in comparison with glial, endothelial and neuronal cell markers revealed co-localization of von Willebrand factor with β- dystroglycan. Its expression at the endothelial-glial interface was preserved in dystrophin isoformdeficient brain from mdx and mdx-3cv mice. In addition, chemical crosslinking revealed that the Dp71 isoform exists in mdx brain predominantly as a monomer. Conclusions: This suggests an association of β-dystroglycan with membranes at the vascular-glial interface in the forebrain. In contrast to dystrophic skeletal muscle fibres, dystrophin deficiency does not trigger a reduction of all dystroglycans in the brain, and utrophins may partially compensate for the lack of brain dystrophins. Abnormal oligomerization of the dystrophin isoform Dp71 might be involved in the pathophysiological mechanisms underlying abnormal brain functions.

    Item Type: Article
    Additional Information: (c) 2001 Culligan et al, licensee BioMed Central Ltd. This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
    Keywords: Brain; dystrophin-glycoprotein complex; beta-dystroglycan; impaired oligomerization; Dp71; utrophins; animal models; muscular dystrophy;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7338
    Identification Number: https://doi.org/10.1186/1471-2121-2-2
    Depositing User: Paul Dowling
    Date Deposited: 12 Aug 2016 15:39
    Journal or Publication Title: BMC Cell Biology
    Publisher: BioMed Central
    Refereed: Yes
    Funders: Health Research Board (HRB), Enterprise Ireland, Royal Society, London, Royal Irish Academy
    URI:

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