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dc.contributor.supervisor Triggs-Raine, Barbara (Biochemistry and Medical Genetics) en_US
dc.contributor.author Chowdhury, Biswajit
dc.date.accessioned 2016-03-11T20:41:17Z
dc.date.available 2016-03-11T20:41:17Z
dc.date.issued 2013 -01 en_US
dc.date.issued 2016-01 en_US
dc.date.issued 2016-02 en_US
dc.identifier.citation Chowdhury, B., Hemming, R., Hombach-Klonisch, S., Flamion, B. and Triggs-Raine, B. (2013) Murine hyaluronidase 2 deficiency results in extracellular hyaluronan accumulation and severe cardiopulmonary dysfunction. J. Biol. Chem. 288, 520-528. doi:10.1074/jbc.M112.393629; 10.1074/jbc.M112.393629 en_US
dc.identifier.citation Chowdhury, B., Hemming, R., Faiyaz, S. and Triggs-Raine, B. (2016) Hyaluronidase 2 (HYAL2) is expressed in endothelial cells, as well as some specialized epithelial cells, and is required for normal hyaluronan catabolism. Histochem. Cell Biol. 145, 53-66. doi:10.1007/s00418-015-1373-8 [doi] en_US
dc.identifier.citation Chowdhury, B., Xiang, B., Muggenthaler, M., Dolinsky, V. W. and Triggs-Raine, B. (2016) Hyaluronidase 2 deficiency is a molecular cause of cor triatriatum sinister in mice. Int. J. Cardiol. 209, 281-283. doi:S0167-5273(16)30296-0 [pii] en_US
dc.identifier.uri http://hdl.handle.net/1993/31154
dc.description.abstract Hyaluronidase 2 (HYAL2) is a GPI-linked protein that is proposed to initiate the degradation of hyaluronan (HA), a major extracellular matrix component of many vertebrate tissues. Hyal2 knockout (KO) mice displayed craniofacial abnormalities and severe preweaning lethality. 54% of the surviving KOs developed a grossly dilated left or right atrium, requiring euthanasia, by 3 months of age. We hypothesize that the absence of HYAL2 leads to the accumulation of HA in organs/tissues where HA is normally abundant resulting in developmental defects and organs dysfunction. Molecular and histological analysis of HYAL2 KO hearts demonstrated extracellular accumulation of high molecular mass (HMM) HA in the heart valves, myocardium, serum and lungs which was associated with severe cardiopulmonary dysfunction. Further, structural and functional analyses of Hyal2 KO mouse hearts using high-frequency ultrasound revealed atrial dilation accompanied by diastolic dysfunction that was evident as early as 4 weeks of age, and progressed with age. Further, 50% of HYAL2 KO mice exhibited a triatrial heart (cor-triatriatum). Histological analyses revealed that the atrial dilation was the result of excess tissue, and did not correlate with the presence of cor triatrium. Hyal2 KO mice were found to have increased numbers of mesenchymal cells at early stages of development, presumably due to the presence of excess HA, that lead to cardiac dysfunction. Further examination of HYAL2 distribution in a broad range of mouse tissues, and accumulation of HA in its absence demonstrated that HYAL2 is mainly localized to endothelial cells and some specialized epithelial cells, and plays a major role in HMM-HA degradation. These studies demonstrated that HYAL2 is important for HA degradation and organ development. In the longer term, our findings will be valuable for understanding pathologies associated with the disruption of HA catabolism, and potentially in the identification of HYAL2-deficient patients. en_US
dc.publisher The American Society for Biochemistry and Molecular Biology en_US
dc.publisher Springer en_US
dc.publisher Elsevier en_US
dc.rights info:eu-repo/semantics/openAccess
dc.subject Hyaluronan, hyaluronidase 2, extracellular matrix, heart, glycosaminoglycans, matrix degradation, mouse model en_US
dc.title Determining the role of murine hyaluronidase 2 in hyaluronan catabolism en_US
dc.type info:eu-repo/semantics/doctoralThesis
dc.type doctoral thesis en_US
dc.degree.discipline Biochemistry and Medical Genetics en_US
dc.contributor.examiningcommittee Wigle, Jeffrey (Biochemistry and Medical Genetics) Merz, David (Biochemistry and Medical Genetics) Dixon, Ian (Physiology and Pathophysiology) Choy, Francis (Centre for Biomedical Research, University of Victoria) en_US
dc.degree.level Doctor of Philosophy (Ph.D.) en_US
dc.description.note May 2016 en_US


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