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Title: Keratan sulphate metabolism in connective tissue proteoglycans
Author: Kerr, Briedgeen C.
ISNI:       0000 0004 2748 0278
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2005
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The generally accepted structure for KS type I has been proposed to be composed of a pattern of non-sulphated N-acetyl-lactosamine disaccharides located next to the linkage region oligosaccharide, with mono-sulphated N-acetyl-lactosamine in the mid-regions of the KS GAG chain and disulphated N-acetyl-lactosamine disaccharides concentrated towards the non-reducing end of the KS chain (Oeben et al., 1987 Stuhlsatz et al., 1989). The generic structure for KS type II has been reported to occur with a similar pattern but with a predominance of disulphated and occasional interdispersed monosulphated N-acetyl-lactosamine residues present throughout the KS glycosaminoglycan chain (Stuhlsatz et al., 1989). A novel KS monoclonal antibody (mAb) recognising a keratanase-generated KS 'stub' neoepitope was developed and used in conjunction with mAb 5D4 (recognising linear sulphated motifs) to analyse the sulphation pattern of KS from cornea and cartilage. The results of these analyses have demonstrated that KS types I and II chains both contain a combination of differentially sulphated (mono- versus di- versus unsulphated) N-acetyl-lactosamine domains. In the bovine model different tissue sources of KS most likely produce similar varieties of KS disaccharide structures, but that sulphation patterns are more randomly located along the KS chain than previously reported. Two mAbs were also generated to the small leucine rich KS proteoglycans lumican and keratocan. They were used in the identification of low and increased levels of these 'corneal associated'; PGs in musculoskeletal tissue locations with pathology. Collectively the data challenges the generic structure for KS and proposes a range of KS chain structures that are more heterogeneous in nature, even from within the same tissue sources, than previously thought. The work also suggests that the expression of the KSPGs, lumican and keratocan, may be useful biomarkers to detect cellular changes in metabolism that lead to the onset of degenerative joint disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available