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Investigation of abnormal cardiac function in murine models of hypocontractility and hypercontractilityTan, Ju Chiat, Graduate School of Biomedical Engineering, Faculty of Engineering, UNSW January 2006 (has links)
Heart failure has a significant impact on mortality and morbidity. Dilated cardiomyopathy (DCM) is the third most common cause of heart failure and the most common reason for heart transplantation. Familial DCM is known to be caused by mutations in the LMNA gene encoding lamins A and C. New methods to enhance cardiac contractility would be beneficial in the treatment or prevention of heart failure. The focus of this thesis was to evaluate the mechanisms of altered contractility in two mouse models: the LMNA knockout model (homozygous, Lmna-/-; heterozygous, Lmna+/-) generated by targeted deletion of the lmna gene, and the model of enhanced contractility due to cardiac alpha1A-adrenergic receptor (???1A-AR) overexpression (A1A1). Previous studies have found altered nuclear-desmin connections in lamin A/C deficient mice. It was proposed that these alterations result in ???defective force transmission???, which leads to DCM. Studies in this thesis have supported this hypothesis. Studies of isolated single cardiomyocytes from mice aged 4-6 weeks demonstrated abnormal cell morphology and contractile dysfunction in Lmna-/- cardiomyocytes, while Lmna+/- cells showed no overt phenotype. Excitation-contraction coupling experiments and forcecalcium studies in skinned fibers excluded altered calcium kinetics as a primary cause of DCM in this model, but there was evidence of reduced sarcomere numbers and reduced sarcomere lengths as a contributor to reduce force generation in Lmna-/- and Lmna+/- mice. Previous in vivo studies showed that A1A1 mice had enhanced contractility with the absence of hypertrophy. Studies on isolated single cardiomyocytes from A1A1 mice aged 8-12 weeks showed reduced contractility in the absence of ???1A-AR stimulation, but an exaggerated response to ???1A-AR stimulation. In contrast isolated isovolumic Langendorff perfused A1A1 hearts without ???1A-AR stimulation replicated the enhanced contractility observed in vivo. These studies are consistent with down-regulation of contractility due to the hyperactivity of the overexpressed ???1A-AR in vivo, which only becomes evident in isolated cells without ???1A-AR stimulation due to the loss of functional receptor numbers during isolation. Sufficient spontaneously active ???1A-ARs are preserved in the isolated Langendorff heart preparation to ensure maximum contractility driven by increase calcium release.
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Inbreeding effects on physiological responses to chronic hypoxia in mice (Mus musculus) /Berting, Jennifer Irene January 2007 (has links) (PDF)
Thesis (M.S.)--University of North Carolina Wilmington, 2007. / Includes bibliographical references (Leaves: 37-44)
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Studies of Mll-Een fusion gene in a conditional mouse model of human leukemiaTsang, Hon-man. January 2007 (has links)
Thesis (M. Phil.)--University of Hong Kong, 2008. / Also available in print.
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Isolation, characterization, and diagnosis of murine noroviruses, a newly recognized pathogen of miceHsu, Charlie Chun, January 2007 (has links)
Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / "December 2007" The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. Includes bibliographical references.
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Immunological studies of a glycosylation based mouse model of colitis /Brown, Steven J. January 2004 (has links)
Thesis (Ph.D.)--University of Melbourne, Dept. of Gastroenterology and the Immunology Research Centre St. Vincents Hospital & Dept of Medicine, 2004. / Typescript (photocopy). Includes bibliographical references (leaves 309-343).
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Distinct precursors of the dendritic cell subtypes /Naik, Shalin Hemant. January 2006 (has links)
Thesis (Ph.D.)--University of Melbourne, Dept. of Medical Biology, 2006. / Typescript. Includes bibliographical references (leaves 189-208).
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Development of methods for detection and eradication of mouse parvovirus from a laboratory mouse colony /Filipovska-Naumovska, Emilija. January 2007 (has links)
Thesis (Ph.D.)--Murdoch University, 2007. / Thesis submitted to the Division of Health Sciences. Includes bibliographical references (leaves 146-165).
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Studies of Mll-Een fusion gene in a conditional mouse model of human leukemia /Tsang, Hon-man. January 2007 (has links)
Thesis (M. Phil.)--University of Hong Kong, 2008. / Also available online.
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The effects of hypotyroidism, the acute inflammatory response, and caloric restriction on neurogensis and behavior in mice /Stepp, Phillip W., January 2004 (has links)
Thesis (Ph.D.)--University of Missouri-Columbia, 2004. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.
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The effects of hypotyroidism, the acute inflammatory response, and caloric restriction on neurogensis and behavior in miceStepp, Phillip W., January 2004 (has links)
Thesis (Ph.D.)--University of Missouri-Columbia, 2004. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.
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