dc.contributor.author |
Kamand, Lara Adnan. |
dc.date.accessioned |
2013-10-02T09:22:26Z |
dc.date.available |
2013-10-02T09:22:26Z |
dc.date.issued |
2012 |
dc.identifier.uri |
http://hdl.handle.net/10938/9538 |
dc.description |
Thesis (M.S.)--American University of Beirut, Department of Biology, 2013. |
dc.description |
Advisor : Dr. Diana E. Jaalouk, Assistant Professor, Department of Biology--Committee Members : Dr. Rabih S. Talhouk, Professor, Department of Biology ; Dr. Georges Nemer, Associate Professor, Biochemistry and Molecular Genetics ; Dr. Asad Zeidan, Assistant Professor, Anatomy, Cell Biology and Physiology. |
dc.description |
Includes bibliographical references (leaves 72-79) |
dc.description.abstract |
Laminopathies are a group of genetic diseases which result from mutations or altered post translational processing of nuclear envelope (NE)-lamina proteins. Most of these disorders are caused by mutations in the LMNA gene which encodes for the NE proteins lamins A-C that anchor other NE proteins to the nuclear membrane. LMNA mutations are manifested as diverse pathologies affecting a wide range of tissues. To date, the molecular mechanisms underlying the phenotypic diversity in laminopathies have not been deciphered; in particular how mutations in a ubiquitously expressed gene lead to tissue specific phenotypes. Many hypotheses have been proposed of which two stood out namely the “structural hypothesis” and the “gene-regulation hypothesis”. We are interested in the latter theory that proposes that altered tissue-specific gene expression may underlie the development of different disease phenotypes. Mechanosensitive genes are of interest in this context since many laminopathies affect mechanically strained tissues. We hereby hypothesize that there is dual deregulation of the mechanosensitive genes Cav-1(encodes for caveolin-1) and Hic-5 (encodes for hypoxia inducible clone 5) in muscular laminopathies including Emery-Dreifuss Muscular Dystrophy (EDMD) and Dilated Cardiomyopathy (DCM).The objective of this study is to probe the expression of Cav-1 and Hic-5 in mouse embryo fibroblast (MEF) cell lines derived from mice either lacking A-type lamin expression (exhibit an EDMD phenotype) or homozygous for the N195K mutant form (exhibit a DCM phenotype). Real-Time PCR quantification of Cav-1expression at baseline conditions showed a decrease in caveolin-1α transcript expression in Lmna⁻-⁻ and in LmnaN195K-N195KMEFs.However, immunofluorescence staining and Western Blot analysis showed no significant difference in caveolin-1α protein expression in both cell lines in comparison to wild-type controls, but putative differences in caveolin-1α secretion are yet to be examin |
dc.format.extent |
xiv, 79 leaves : ill. (some col.) ; 30 cm. |
dc.language.iso |
eng |
dc.relation.ispartof |
Theses, Dissertations, and Projects |
dc.subject.classification |
T:005780 AUBNO |
dc.subject.lcsh |
Fibroblasts. |
dc.subject.lcsh |
Gene expression. |
dc.subject.lcsh |
Mutation (Biology) |
dc.subject.lcsh |
Molecular genetics. |
dc.subject.lcsh |
Mice -- Embryos. |
dc.subject.lcsh |
Transgenic mice. |
dc.subject.lcsh |
Mice as laboratory animals. |
dc.title |
Deregulated caveolin-1 and Hic-5 expression in mouse embryo fibroblasts lacking A-type lamin and homozygous for the N195K mutant form |
dc.type |
Thesis |
dc.contributor.department |
American University of Beirut. Faculty of Arts and Sciences. Department of Biology. |