Glomerulosclerosis in the Col1a2-deficient mouse model: homotrimer pathogenesis and MMP expression

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Glomerulosclerosis in the Col1a2-deficient mouse model: homotrimer pathogenesis and MMP expression

Please use this identifier to cite or link to this item: http://hdl.handle.net/10355/6155

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dc.contributor.advisor Phillips, Charlotte L. en_US
dc.contributor.author Roberts-Pilgrim, Anna M., 1977- en_US
dc.date.accessioned 2010-02-25T17:47:13Z
dc.date.available 2010-02-25T17:47:13Z
dc.date.issued 2009 en_US
dc.date.submitted 2009 Spring en_US
dc.identifier.other RobertsPilgrimA-050809-D1550 en_US
dc.identifier.uri http://hdl.handle.net/10355/6155
dc.description Title from PDF of title page (University of Missouri--Columbia, viewed on Feb. 20, 2010). en_US
dc.description The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. en_US
dc.description Dissertation advisor: Charlotte L. Phillips. en_US
dc.description Vita. en_US
dc.description Includes bibliographical references. en_US
dc.description Ph. D. University of Missouri--Columbia 2009. en_US
dc.description Dissertations, Academic -- University of Missouri--Columbia -- Biochemistry. en_US
dc.description.abstract The Col1a2-deficient (oim) mouse model exclusively synthesizes homotrimeric type I collagen due to the lack of functional pro [alpha] 2(I) collagen chains. The mouse develops a type I collagen glomerulopathy that has previously been shown to initiate postnatally and progress in a gene dose-dependent manner, accumulating type I collagen within the renal mesangium, resulting in podocyte foot effacement and proteinuria. In this study we examine the pre- and post-translational expression of type I collagen and MMPs -2, -3, and -9 in wildtype, heterozygous and Col1a2-deficient glomeruli to determine whether the pathogenic collagen is homotrimeric in nature, and whether alterations in MMP expression play a role in disease progression. Analysis of whole kidney and isolated glomeruli by immunohistochemistry and CNBr peptide mapping suggest that homotrimer is the accumulating type I collagen isotype in sclerotic glomeruli of both affected and heterozygous mice. Steady state MMPs-2, and -3 mRNA levels exhibited significant increases by three months of age, with corresponding protein increases compared to age-matched wildtype mice. Steady state MMP-9 mRNA levels significantly increased by three months of age, but MMP-9 protein expression was significantly decreased. Our findings suggest that upregulation of MMPs-2 and -3 expression is not sufficient to prevent homotrimeric type I collagen deposition and that their induction does not appear to be an initiating event, but may represent a secondary wound response. en_US
dc.format.extent x, 156 pages en_US
dc.language.iso en_US en_US
dc.publisher University of Missouri--Columbia en_US
dc.subject.lcsh Kidney glomerulus -- Diseases en_US
dc.subject.lcsh Cytoskeletal proteins en_US
dc.title Glomerulosclerosis in the Col1a2-deficient mouse model: homotrimer pathogenesis and MMP expression en_US
dc.type Thesis en_US
thesis.degree.discipline Biochemistry en_US
thesis.degree.grantor University of Missouri--Columbia en_US
thesis.degree.name Ph. D. en_US
thesis.degree.level Doctoral en_US
dc.identifier.oclc 522384466 en_US
dc.relation.ispartofcommunity University of Missouri-Columbia. Graduate School. Theses and Dissertations. Dissertations. 2009 Dissertations
dc.relation.ispartofcollection 2009 Freely available dissertations (MU)


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