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dc.contributor.supervisor Triggs-Raine, Barbara (Biochemistry and medical genetics) en_US
dc.contributor.author Gushulak, Lara E. M.
dc.date.accessioned 2012-03-26T19:25:04Z
dc.date.available 2012-03-26T19:25:04Z
dc.date.issued 2012-03-26
dc.identifier.uri http://hdl.handle.net/1993/5208
dc.description.abstract Hyaluronan, a member of the glycosaminoglycan family, is a critical component of the extracellular matrix. A model for hyaluronan degradation has been advanced that invokes the activity of both hyaluronidases and exoglycosidases. However, no in vivo studies have been done to determine the extent to which these enzymes contribute to hyaluronan breakdown. Herein, we have used several mouse models to investigate the contributions of the exoglycosidase, β-hexosaminidase, and the endoglycosidase, hyaluronidase 1, to the lysosomal degradation of hyaluronan. We employed immunohistochemistry and fluorophore assisted carbohydrate electrophoresis to determine the degree of hyaluronan accumulation in mice deficient in one or both enzyme activities. β-Hexosaminidase-deficient mice displayed only low levels of hyaluronan accumulation, limited to the liver and lymph node. The distribution and levels of hyaluronan in hyaluronidase 1-deficient mice were similar to that observed in β-hexosaminidase-deficient mice. Interestingly, extensive global hyaluronan accumulation was present in mice deficient in both enzymes, with the highest levels found in liver and lymph node. Chondroitin, a glycosaminoglycan similar in structure to hyaluronan, was also broadly accumulating in mice deficient in both enzymes. Further, the accumulation of chondroitin sulphate derivatives was detected in mice deficient in both enzymes, as well as in β-hexosaminidase-deficient mice, indicating that both enzymes play a significant role in chondroitin sulphate breakdown. Extensive accumulation of hyaluronan and chondroitin when both enzymes are lacking suggests β-hexosaminidase and hyaluronidase 1 are functionally redundant in hyaluronan and chondroitin breakdown, as broad extensive accumulation was not observed in mice deficient in only one of these enzymes. en_US
dc.subject Glycobiology en_US
dc.title The contribution of β-hexosaminidase and hyaluronidase 1 to hyaluronan turnover en_US
dc.degree.discipline Biochemistry and Medical Genetics en_US
dc.contributor.examiningcommittee Pind, Steve (Biochemistry and medical Genetics) Hombach-Klonisch, Sabine (Human Anatomy and Cell Science) en_US
dc.degree.level Master of Science (M.Sc.) en_US
dc.description.note May 2012 en_US


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