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dc.contributor.advisorPhillips, Charlotte L.en_US
dc.contributor.authorRoberts-Pilgrim, Anna M., 1977-en_US
dc.date.issued2009eng
dc.date.submitted2009 Springen_US
dc.descriptionTitle from PDF of title page (University of Missouri--Columbia, viewed on Feb. 20, 2010).en_US
dc.descriptionThe 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.descriptionDissertation advisor: Charlotte L. Phillips.en_US
dc.descriptionVita.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.descriptionPh. D. University of Missouri--Columbia 2009.en_US
dc.descriptionDissertations, Academic -- University of Missouri--Columbia -- Biochemistry.en_US
dc.description.abstractThe 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.extentx, 156 pagesen_US
dc.identifier.oclc522384466en_US
dc.identifier.otherRobertsPilgrimA-050809-D1550en_US
dc.identifier.urihttp://hdl.handle.net/10355/6155
dc.publisherUniversity of Missouri--Columbiaen_US
dc.relation.ispartofcollection2009 Freely available dissertations (MU)
dc.relation.ispartofcommunityUniversity of Missouri-Columbia. Graduate School. Theses and Dissertations. Dissertations. 2009 Dissertations
dc.source.originalSubmitted by University of Missouri--Columbia Graduate School.eng
dc.subject.lcshKidney glomerulus -- Diseasesen_US
dc.subject.lcshCytoskeletal proteinsen_US
dc.titleGlomerulosclerosis in the Col1a2-deficient mouse model: homotrimer pathogenesis and MMP expressionen_US
dc.typeThesisen_US
thesis.degree.disciplineBiochemistry (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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