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dc.contributor.advisorRichard Lee.en_US
dc.contributor.authorHsiao, Janet, 1981-en_US
dc.contributor.otherHarvard University--MIT Division of Health Sciences and Technology.en_US
dc.date.accessioned2005-09-27T18:11:40Z
dc.date.available2005-09-27T18:11:40Z
dc.date.copyright2004en_US
dc.date.issued2004en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/28759
dc.descriptionThesis (M. Eng.)--Harvard-MIT Division of Health Sciences and Technology, 2004.en_US
dc.descriptionIncludes bibliographical references (p. 54-55).en_US
dc.description.abstract(cont.) nucleus and at the nuclear surface.en_US
dc.description.abstractMutations in the lamin A/C gene (Lmna) and the lamin-associated protein emerin gene (EM) cause a variety of human diseases including Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, familial partial lipodystrophy, Charcot-Marie-Tooth Neuropathy and Hutchinson-Gilford progeria syndrome. The molecular mechanisms underlying the varied phenotypes are unknown, and both a mechanical stress hypothesis and an altered gene expression hypothesis have been proposed to explain the tissue specific effects observed in laminopathies. To investigate the role of emerin in mechanotransduction, lamin A/C deficient (Lmna⁻/⁻) fibroblasts, and emerin deficient (EM⁻/y) fibroblasts were studied for nuclear mechanical properties, cytoskeletal stiffness, and mechanical strain-induced signaling. EM⁻/y fibroblasts exhibited similar cell sensitivity, nuclear and cytoskeletal properties compared to wild type cells under stress and strain. Interestingly, both Lmna⁻/⁻ and EM⁻/y fibroblasts had impaired mechanotransduction, characterized by attenuated expression of the mechanosensitive genes egr-1, iex-1, and txnip in response to mechanical stimulation. In addition, NF-rB signaling appeared disturbed in Lmna⁻/⁻ cells, but normal in EM⁻/y fibroblasts. The relationship between changes in cytoskeletal stiffness recently discovered in Lmna⁻/⁻ cells and nuclear mechanics under strain was explored using a computational finite elemental model. Analysis of the several models using variations in material properties and cell geometry revealed that nuclear shape, material properties of the cytoskeleton and nucleus, as well as the size and location of strain application on the cell are important parameters in determining the magnitude of stress and strain within theen_US
dc.description.statementofresponsibilityby Janet Hsiao.en_US
dc.format.extent71 p.en_US
dc.format.extent3831344 bytes
dc.format.extent3838379 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsM.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582
dc.subjectHarvard University--MIT Division of Health Sciences and Technology.en_US
dc.titleEmerin and inherited diseaseen_US
dc.typeThesisen_US
dc.description.degreeM.Eng.en_US
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technology
dc.identifier.oclc59823266en_US


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