{"id":{"repo_id":"missouri","oai_identifier":"oai:mospace.umsystem.edu:10355/6155"},"canonical_url":"https://search.dev.ndltd.org/etd/missouri/oai:mospace.umsystem.edu:10355/6155","repository":{"repo_id":"missouri","name":"University of Missouri","base_url":"https://mospace.umsystem.edu/oai/request"},"display":{"title":"Glomerulosclerosis in the Col1a2-deficient mouse model : homotrimer pathogenesis and MMP expression","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Roberts-Pilgrim, Anna M., 1977-"],"institution":"University of Missouri--Columbia","degree_name":"Ph. D.","degree_level":"Doctoral","degree_discipline":"Biochemistry (MU)","degree_department":null,"school":null,"contributors":[],"advisors":["Phillips, Charlotte L."],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009","date_published":"2009","updated_at":"2026-07-24T03:08:32Z","subjects":[],"languages":["eng","English"],"rights":["OpenAccess."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.32469/10355/6155"],"render_values":[{"text":"https://doi.org/10.32469/10355/6155","href":"https://doi.org/10.32469/10355/6155","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/10355/6155","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Phillips, Charlotte L."]},{"key":"dc:creator","label":"Author","values":["Roberts-Pilgrim, Anna M., 1977-"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2010-02-25T17:47:13Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2010-02-25T17:47:13Z"]},{"key":"dc:date.issued","label":"Date","values":["2009"]},{"key":"dc:publisher","label":"Institution","values":["University of Missouri--Columbia"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry (MU)"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph. 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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."]},{"key":"dc:source","label":"Dc Source","values":["Submitted by University of Missouri--Columbia Graduate School."]},{"key":"dc:title","label":"Title","values":["Glomerulosclerosis in the Col1a2-deficient mouse model : homotrimer pathogenesis and MMP expression"]}]}],"canonical_facts":{"dc:contributor.advisor":["Phillips, Charlotte L."],"dc:creator":["Roberts-Pilgrim, Anna M., 1977-"],"dc:date.accessioned":["2010-02-25T17:47:13Z"],"dc:date.available":["2010-02-25T17:47:13Z"],"dc:date.issued":["2009"],"dc:description":["Title from PDF of title page (University of Missouri--Columbia, viewed on Feb. 20, 2010).","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.","Dissertation advisor: Charlotte L. 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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. 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