Show simple item record

dc.contributor.authorAckroyd, M.R.
dc.contributor.authorWhitmore, C.
dc.contributor.authorPrior, S.
dc.contributor.authorKaluarachchi, M.
dc.contributor.authorNikolic, M.
dc.contributor.authorMayer, U.
dc.contributor.authorMuntoni, F.
dc.contributor.authorBrown, S.C.
dc.date.accessioned2013-09-17T12:15:16Z
dc.date.available2013-09-17T12:15:16Z
dc.date.issued2011-09-07
dc.identifier.citationAckroyd , M R , Whitmore , C , Prior , S , Kaluarachchi , M , Nikolic , M , Mayer , U , Muntoni , F & Brown , S C 2011 , ' Fukutin-related protein alters the deposition of laminin in the eye and brain ' , Journal of Neuroscience , vol. 31 , no. 36 , pp. 12927-12935 . https://doi.org/10.1523/JNEUROSCI.2301-11.2011
dc.identifier.issn0270-6474
dc.identifier.otherPURE: 1795860
dc.identifier.otherPURE UUID: 2c573172-8467-4c8e-baa4-3b5c80443ebd
dc.identifier.otherScopus: 80052555220
dc.identifier.urihttp://hdl.handle.net/2299/11615
dc.description.abstractMutations in fukutin-related protein (FKRP) are responsible for acommongroup of muscular dystrophies ranging from adult onset limb girdle muscular dystrophies to severe congenital forms with associated structural brain involvement. The defining feature of this group of disorders is the hypoglycosylation of α-dystroglycan and its inability to effectively bind extracellular matrix ligands such as laminin α 2. However, α-dystroglycan has the potential to interact with a number of laminin isoforms many of which are basement membrane/ tissue specific and developmentally regulated. To further investigate this we evaluated laminin α-chain expression in the cerebral cortex and eye of our FKRP knock-down mouse (FKRP ). These mice showed a marked disturbance in the deposition of laminin α-chains including α1, α2, α4, and α5, although only laminin α1-and γ1-chain mRNA expression was significantly upregulated relative to controls. Moreover, there was a diffuse pattern of laminin deposition below the pial surface which correlated with an abrupt termination of many of the radial glial cells. This along with the pial basement membrane defects, contributed to the abnormal positioning of both early-and late-born neurons. Defects in the inner limiting membrane of the eye were associated with a reduction of laminin α1 demonstrating the involvement of the α-dystroglycan:laminin α1 axis in the disease process. These observations demonstrate for the first time that a reduction in Fkrp influences the ability of tissue-specific forms of α-dystroglycan to direct the deposition of several laminin isoforms in the formation of different basement membranesen
dc.format.extent9
dc.language.isoeng
dc.relation.ispartofJournal of Neuroscience
dc.titleFukutin-related protein alters the deposition of laminin in the eye and brainen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionPharmacology and Clinical Science Research
dc.contributor.institutionAgriculture, Food and Veterinary Sciences
dc.contributor.institutionBiochemistry and Bioinformatics
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=80052555220&partnerID=8YFLogxK
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1523/JNEUROSCI.2301-11.2011
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record