Cloning and characterization of fibrillin 2, a new extracellular matrix protein.
Item
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Title
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Cloning and characterization of fibrillin 2, a new extracellular matrix protein.
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Identifier
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AAI9510744
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identifier
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9510744
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Creator
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Zhang, Hui.
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Contributor
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Adviser: Francesco Ramirez
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Date
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1994
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Molecular | Biology, Genetics | Biology, Cell
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Abstract
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Microfibrils are incompletely characterized structures of the extracellular matrix (ECM), that in association with elastin participate in the formation of the elastic fibers. The gene coding for the major component of microfibrils, fibrillin, has recently been cloned. This fibrillin gene (FBN1) has also been shown to be responsible for Marfan syndrome (MFS), a connective tissue disorder with skeletal, cardiovascular and ocular manifestations. During the cloning of FBN1, a structurally homologous gene (FBN2) was unexpectedly identified. Genetic linkage analysis revealed that FBN2 is tightly linked to an MFS-related disorder, congenital contractual arachnodactyly (CCA). It was therefore proposed that FBN2 produces a protein product that is structurally and functionally related to that of FBN1. The main goal of this thesis project was to test this hypothesis by characterizing the FBN2 product.;First, the FBN2 transcript was cloned in its entirety, and the deduced amino acid sequence was shown to be structurally related to the FBN1 product. Second, antibodies raised against a peptide with FBN2 specific sequence identified the protein encoded by the FBN2 gene (Fib2) in the extracellular microfibrils. The antibodies also revealed that Fib2 is preferentially located in elastin-rich areas of the connective tissues. To confirm and extend this observation, murine FBN1 and FBN2 cDNA probes were used to establish the pattern of fibrillin expression during mouse embryogenesis by in situ hybridization. These revealed that the FBN1 and FBN2 genes are differentially expressed, both in term of developmental stages and tissue localization. The differential expression of the fibrillin genes strongly suggests that there are differences in microfibril composition and function in various developmental stages and tissues. The postulated differences are consistent with the distinct pathologies resulting from defects in the two fibrillin proteins. This work lays the foundation for more in depth studies elucidating the function and regulation of the fibrillins, and clarifying the role of these proteins in microfibril assembly and elastic tissue formation.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
